58 results on '"Daniel Saiz-Sanchez"'
Search Results
2. HUNTINGTIN DISTRIBUTION, GLIAL INVOLVEMENT AND COPATHOLOGIES IN THE HUMAN AMYGDALA IN HUNTINGTON’S DISEASE
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Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, Alino Martinez-Marcos, Alberto Rábano, Julia Vaamonde-Gamo, and Isabel Ubeda-Banon
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2023
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3. ROLE OF ANXA2, HSP90AA1 AND PTK2B IN SYNAPTIC HOMEOSTASIS THROUGH MICROGLIAL CELLS IN THE HUMAN ENTORHINAL CORTEX IN ALZHEIMER’S DISEASE.
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Veronica Astillero-Lopez, Sandra Villar-Conde, Melania Gonzalez-Rodriguez, Alicia Flores-Cuadrado, Isabel Ubeda-Banon, Daniel Saiz-Sanchez, and Alino Martinez-Marcos
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2023
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4. Neuronal and glial characterization in the rostrocaudal axis of the human anterior olfactory nucleus: Involvement in Parkinson’s disease
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Sandra Villar-Conde, Veronica Astillero-Lopez, Melania Gonzalez-Rodriguez, Daniel Saiz-Sanchez, Isabel Ubeda-Banon, Alicia Flores-Cuadrado, and Alino Martinez-Marcos
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olfaction ,olfactory bulb ,olfactory system ,Lewy pathology ,stereology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Human anatomy ,QM1-695 - Abstract
Hyposmia is one of the prodromal symptoms of Parkinson’s disease (PD) and a red flag in clinical diagnosis. Neuropathologically, this sign correlates with α-synuclein involvement in the anterior olfactory nucleus (AON). Neurodegeneration, microgliosis, and astrogliosis in AON are poorly studied, and bulbar AON is the focus of these studies with contradictory results. Additionally, male sex is a risk marker for developing PD, but sexual dimorphism of neural and glial populations in the AON has rarely been considered. The aim of this study was to analyze the density of NeuN, Iba-1, GFAP, and Lewy bodies (LBs), as well as the relationship of these cell type markers with pathology along the rostrocaudal axis of the AON (bulbar, retrobulbar, cortical anterior, and posterior divisions). Cavalieri, optical fractionator, and area fraction fractionator stereological approaches were used for the volume, cell populations and LBs densities, area fraction, and percentage of overlap. Iba-1 and α-syn intensities were measured using ImageJ. In non-PD (NPD) cases, the volume was lower in the AON at the extremes of the rostrocaudal axis than in the intermediate divisions. Cortical anterior AON volume decreased in PD compared with NPD cases. NeuN density decreased rostrocaudally in AON portions in NPD and PD cases. This occurred similarly in Iba-1 but only in PD samples. Iba-1 intensity significantly increased in bulbar AON between PD and NPD. No changes were found in astrocytes. Eight percent of NeuN, 0.1% of Iba-1, and 0.1% of GFAP areas overlapped with LBs area along the AON portions. The data indicate that bulbar AON, which is the most rostral portion in this axis, could play a major role in the pathology. This could be related to the larger area occupied by LBs in these divisions.
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- 2022
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5. Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson’s disease
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Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, Alicia Mohedano-Moriano, Elena Lamas-Cenjor, Victor Leon-Olmo, Alino Martinez-Marcos, and Isabel Ubeda-Bañon
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson’s disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for α-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, α-synucleinopathy (α-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. α-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson’s disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson’s disease.
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- 2021
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6. The human olfactory system in two proteinopathies: Alzheimer’s and Parkinson’s diseases
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Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, Alicia Flores-Cuadrado, Ernesto Rioja-Corroto, Melania Gonzalez-Rodriguez, Sandra Villar-Conde, Veronica Astillero-Lopez, Juan Pablo Cabello-de la Rosa, Maria Jose Gallardo-Alcañiz, Julia Vaamonde-Gamo, Fernanda Relea-Calatayud, Lucia Gonzalez-Lopez, Alicia Mohedano-Moriano, Alberto Rabano, and Alino Martinez-Marcos
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α-Synuclein ,Amyloid-β ,Anterior olfactory nucleus, hyposmia ,Tau protein ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease, and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus) of network dysfunction in Alzheimer’s and Parkinson’s diseases.
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- 2020
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7. Neurodegeneration and contralateral α-synuclein induction after intracerebral α-synuclein injections in the anterior olfactory nucleus of a Parkinson’s disease A53T mouse model
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Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, Alicia Mohedano-Moriano, Alino Martinez-Marcos, and Isabel Ubeda-Bañon
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α-Synucleinopathy ,Astroglia ,Microglia ,Neurodegeneration ,Non-motor symptoms ,Olfaction ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Parkinson’s disease is characterized by a proteinopathy that includes aggregates of α-synuclein. A recent hypothesis proposes a prion-like spreading mechanism for this α-synucleinopathy. Early neuropathological deposits occur, among others, in the anterior olfactory nucleus (AON). This study investigates the anterograde and/or retrograde transmissibility of exogenous α-synuclein inoculated in the right AON of the A53T model of Parkinson’s disease and wild-type mice as well as neuronal and glial involvement. Seven experimental groups were established: wild-type injected with tracers; A53T mice injected with either α-synuclein or saline 2 months beforehand; wild-type injected with either α-synuclein or saline 2 months beforehand; and wild-type injected with either α-synuclein or saline 4 months beforehand. Weight and behavioral changes were analyzed. Immunohistochemistry against α-synuclein, NeuN, Iba-1 and GFAP was performed. Volume and marker distributions in the olfactory bulb (OB), AON and piriform cortex were analyzed using unbiased stereology. The behavioral analyses reveal higher levels of hyperactivity in transgenic as compared to wild-type mice. Tract-tracing experiments show that the main contralateral afferent projections to the dorsal AON come from the AON and secondarily from the OB. In saline-injected transgenic animals, α-synuclein expression in the OB and the AON is higher in the left hemisphere than in the right hemisphere, which could be due to basal interhemispheric differences. α-synuclein injection could provoke a significant increase in the left hemisphere of the transgenic mice’s OB, compared to saline-injected animals. Neuronal loss was observed in saline-injected transgenic mice relative to the saline-injected wild-type group. There were no overall differences in neuron number following injection of α-synuclein into either wild-type or transgenic mice, however some neuron loss was apparent in specific regions of α-synuclein injected wild-types. Microglia labeling appeared to be correlated with surgery-induced inflammation. Astroglial labeling was higher in transgenic animals, which could be due to endogenous α-synucleinopathy. This study suggests α-synucleinopathy induction, via retrograde and contralateral projections, within the olfactory system of transgenic animals.
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- 2019
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8. Somatostatin, Olfaction, and Neurodegeneration
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Daniel Saiz-Sanchez, Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Melania Gonzalez-Rodriguez, Sandra Villar-Conde, Veronica Astillero-Lopez, and Alino Martinez-Marcos
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α-synuclein ,amyloid-β ,anterior olfactory nucleus ,hyposmia ,tau ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders in aging. Hyposmia has been described as an early symptom that can precede cognitive and motor deficits by decades. Certain regions within the olfactory system, such as the anterior olfactory nucleus, display the neuropathological markers tau and amyloid-β or α-synuclein from the earliest stages of disease progression in a preferential manner. Specific neuronal subpopulations, namely those expressing somatostatin (SST), are preferentially affected throughout the olfactory and limbic systems. SST is a neuropeptide present in a subpopulation of GABAergic interneurons throughout the brain and its main function is to inhibit principal neurons and/or other interneurons. It has been reported that SST expression is reduced by 50% in Alzheimer’s disease and that it is related to the formation of Aβ oligomers. The mechanisms underlying the preferential vulnerability of SST-expressing neurons in Alzheimer’s disease (and, to a minor extent, in Parkinson’s disease) are not known but analysis of the available data could shed light on their etiology. This short review aims to update the knowledge of functional features of somatostatin within the olfactory system and its role in olfactory deficits during neurodegeneration.
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- 2020
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9. Neurodegeneration and Astrogliosis in the Human CA1 Hippocampal Subfield Are Related to hsp90ab1 and bag3 in Alzheimer’s Disease
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Melania Gonzalez-Rodriguez, Sandra Villar-Conde, Veronica Astillero-Lopez, Patricia Villanueva-Anguita, Isabel Ubeda-Banon, Alicia Flores-Cuadrado, Alino Martinez-Marcos, and Daniel Saiz-Sanchez
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amyloid-β ,tau ,GFAP ,autophagy ,cavalieri ,optical fractionator ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is characterized by executive dysfunction and memory impairment mediated by the accumulation of extracellular amyloid-β peptide (Aβ) and intracellular hyperphosphorylated tau protein. The hippocampus (HIPP) is essential for memory formation and is involved in early stages of disease. In fact, hippocampal atrophy is used as an early biomarker of neuronal injury and to evaluate disease progression. It is not yet well-understood whether changes in hippocampal volume are due to neuronal or glial loss. The aim of the study was to assess hippocampal atrophy and/or gliosis using unbiased stereological quantification and to obtain hippocampal proteomic profiles related to neurodegeneration and gliosis. Hippocampal volume measurement, stereological quantification of NeuN-, Iba-1- and GFAP-positive cells, and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) analysis were performed in AD and non-AD cases. Reduced hippocampal volume was identified using the Cavalieri probe, particularly in the CA1 region, where it correlated with neuronal loss and astrogliosis. A total of 102 downregulated and 47 upregulated proteins were identified in the SWATH-MS analysis after restrictive filtering based on an FC > 1.5 and p value < 0.01. The Hsp90 family of chaperones, particularly BAG3 and HSP90AB1, are closely related to astrocytes, indicating a possible role in degrading Aβ and tau through chaperone-mediated autophagy.
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- 2021
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10. Somatostatin and Astroglial Involvement in the Human Limbic System in Alzheimer’s Disease
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Melania Gonzalez-Rodriguez, Veronica Astillero-Lopez, Patricia Villanueva-Anguita, M. Eugenia Paya-Rodriguez, Alicia Flores-Cuadrado, Sandra Villar-Conde, Isabel Ubeda-Banon, Alino Martinez-Marcos, and Daniel Saiz-Sanchez
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Alzheimer’s disease ,somatostatin ,hippocampus ,olfactory bulb ,astroglia ,stereology ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly. Progressive accumulation of insoluble isoforms of amyloid-β peptide (Aβ) and tau protein are the major neuropathologic hallmarks, and the loss of cholinergic pathways underlies cognitive deficits in patients. Recently, glial involvement has gained interest regarding its effect on preservation and impairment of brain integrity. The limbic system, including temporal lobe regions and the olfactory bulb, is particularly affected in the early stages. In the early 1980s, the reduced expression of the somatostatin neuropeptide was described in AD. However, over the last three decades, research on somatostatin in Alzheimer’s disease has been scarce in humans. Therefore, the aim of this study was to stereologically quantify the expression of somatostatin in the human hippocampus and olfactory bulb and analyze its spatial distribution with respect to that of Aβ and au neuropathologic proteins and astroglia. The results indicate that somatostatin-expressing cells are reduced by 50% in the hippocampus but are preserved in the olfactory bulb. Interestingly, the coexpression of somatostatin with the Aβ peptide is very common but not with the tau protein. Finally, the coexpression of somatostatin with astrocytes is rare, although their spatial distribution is very similar. Altogether, we can conclude that somatostatin expression is highly reduced in the human hippocampus, but not the olfactory bulb, and may play a role in Alzheimer’s disease pathogenesis.
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- 2021
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11. Differential Effects of Parkinson’s Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus
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Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, and Alino Martinez-Marcos
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calcium binding protein ,non-motor symptoms ,olfaction ,somatostatin ,α-synucleinopathy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Human anatomy ,QM1-695 - Abstract
Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease’s progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON. First, we determined the expression of the calcium binding interneuron markers, calretinin, calbindin and parvalbumin, as well as non-calcium binding interneuron marker, somatostatin, in neuronal cell bodies alone (cells/mm2) and in neuronal cell bodies and neurites (% of area fraction) of post-mortem tissue from PD cases and age-matched controls (n = 4 for each) by immunofluorescent confocal microscopy. Results indicated that parvalbumin expression was upregulated in neuronal cell bodies throughout the anterior olfactory nucleus of PD cases compared with controls. Furthermore, there was increased calbindin, calretinin and parvalbumin expression in the cell bodies and neurites of neurons in the retrobulbar division and also increased parvalbumin expression in the neurites of neurons in the cortical division; calretinin expression was also increased in neuronal cell bodies and neurites in the cortical posterior division. Second, we analyzed the co-localization of the above markers with α-synuclein, with results indicating that α-synuclein co-localized with the calcium-binding proteins, but only partially with somatostatin. Taken together, these results indicate differential expression levels among different neural markers in the divisions of the AON in PD cases and point to several possibilities, among them: possible neuroprotective mechanisms of calcium-binding proteins against α-synuclein; and the differential involvement of somatostatin in α-synuclein-positive cell bodies and neurites.
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- 2017
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12. Correction to: Novel interaction between neurotrophic factor-α1/carboxypeptidase E and serotonin receptor, 5-HTR1E, protects human neurons against oxidative/neuroexcitotoxic stress via β-arrestin/ERK signaling
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Vinay Kumar Sharma, Xuyu Yang, Soo-Kyung Kim, Amirhossein Mafi, Daniel Saiz-Sanchez, Patricia Villanueva-Anguita, Lan Xiao, Asuka Inoue, William A. Goddard, Y. Peng Loh, and Leila Toulabi
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Pharmacology ,Cellular and Molecular Neuroscience ,Molecular Medicine ,Cell Biology ,Molecular Biology - Abstract
In the published article, the author name Leila Toulabi was missed during the proof stage and it has been now updated. Section on Cellular Neurobiology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, 49, Convent Drive, Bldg 49, Rm 6A‑10, Bethesda, MD 20892, USA. The original article has been updated.
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- 2023
13. The Importance of Optional Practical Anatomy Courses for Undergraduate Speech Therapy Students
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Begoña Polonio-Lopez, Francisco Martín-Rodríguez, Daniel Saiz-Sanchez, Juan José Criado-Álvarez, José Luis Martín-Conty, Javier Aceituno-Gómez, Jaime González-González, Alicia Mohedano-Moriano, Alicia Flores-Cuadrado, Diana Monforte Perez, Carmen Romo-Barrientos, and Antonio Viñuela
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0301 basic medicine ,Embryology ,Students, Medical ,Histology ,020205 medical informatics ,Training course ,02 engineering and technology ,Speech Therapy ,Speech therapy ,03 medical and health sciences ,Health science ,Professional life ,ComputingMilieux_COMPUTERSANDEDUCATION ,0202 electrical engineering, electronic engineering, information engineering ,Humans ,Curriculum ,Health professionals ,Undergraduate education ,General Medicine ,Anatomy ,Anatomical knowledge ,030101 anatomy & morphology ,Psychology ,Education, Medical, Undergraduate - Abstract
An in-depth understanding of the anatomy discipline is essential for the work of healthcare professionals. In recent decades, the content and time of teaching anatomy have decreased in all health science degrees. The aim of this study was to look for alternatives for compensating the reduction of the teaching of anatomy by supplementing students with a practical training course and to know evaluations of the course given by students enrolled in the degree in Speech Therapy and its impact on their academic results. All students (100%) positively evaluated having acquired skills and attitudes for their future professional life. The majority of the students (95.8%) believed that their knowledge was acceptable; 97.2% of the students thought they would have the possibility to apply their acquired anatomical knowledge as professionals; 98.5% were satisfied with the voluntary course; and finally, the percentage of students that passed the "Anatomophysiology of language and voice organs" course increased from previous academic years. Optional (theoretical/practical) undergraduate courses can be used in parallel to overcome the devaluation of anatomical studies in new curricula. The optional undergraduate anatomy course in the Speech Therapy program has been positively evaluated because it stimulated students' motivation and appealed to their interest in anatomy. Students considered that these courses would help them in their training and they could put what they had learned into practice in their future professions. However, very little evidence for the impact of optional practical courses exists, yet it could be an efficient method to increase anatomical knowledge.
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- 2021
14. Novel interaction between neurotrophic factor-α1/carboxypeptidase E and serotonin receptor, 5-HTR1E, protects human neurons against oxidative/neuroexcitotoxic stress via β-arrestin/ERK signaling
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Vinay Kumar Sharma, Xuyu Yang, Soo-Kyung Kim, Amirhossein Mafi, Daniel Saiz-Sanchez, Patricia Villanueva-Anguita, Lan Xiao, Leila Toulabi, Asuka Inoue, William A. Goddard, and Y. Peng Loh
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Cell Survival ,MAP Kinase Signaling System ,Cytotoxicity ,Neurotoxins ,Down-Regulation ,Molecular Dynamics Simulation ,Hippocampus ,Mice ,Cellular and Molecular Neuroscience ,GPCR ,Protein Domains ,Cyclic AMP ,Animals ,Humans ,Nerve Growth Factors ,Phosphorylation ,Cyclic AMP Response Element-Binding Protein ,Molecular Biology ,beta-Arrestins ,Neurons ,Pharmacology ,β-arrestin ,Carboxypeptidase H ,Cell Biology ,Neuroprotection ,Molecular Docking Simulation ,Oxidative Stress ,HEK293 Cells ,Neuroprotective Agents ,Receptors, Serotonin ,Molecular Medicine ,Original Article ,Protein Binding - Abstract
Protecting neurons from death during oxidative and neuroexcitotoxic stress is key for preventing cognitive dysfunction. We uncovered a novel neuroprotective mechanism involving interaction between neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor with no previously known neurological function. Co-immunoprecipitation and pull-down assays confirmed interaction between NFα1/CPE and 5-HTR1E and 125I NF-α1/CPE-binding studies demonstrated saturable, high-affinity binding to 5-HTR1E in stably transfected HEK293 cells (Kd = 13.82 nM). Treatment of 5-HTR1E stable cells with NF-α1/CPE increased pERK 1/2 and pCREB levels which prevented a decrease in pro-survival protein, BCL2, during H2O2-induced oxidative stress. Cell survival assay in β-arrestin Knockout HEK293 cells showed that the NF-α1/CPE-5-HTR1E-mediated protection against oxidative stress was β-arrestin-dependent. Molecular dynamics studies revealed that NF-α1/CPE interacts with 5-HTR1E via 3 salt bridges, stabilized by several hydrogen bonds, independent of the serotonin pocket. Furthermore, after phosphorylating the C-terminal tail and intracellular loop 3 (ICL3) of NF-α1/CPE-5-HTR1E, it recruited β-arrestin1 by forming numerous salt bridges and hydrogen bonds to ICL2 and ICL3, leading to activation of β-arrestin1. Immunofluorescence studies showed 5-HTR1E and NF-α1/CPE are highly expressed and co-localized on cell surface of human hippocampal neurons. Importantly, knock-down of 5-HTR1E in human primary neurons diminished the NF-α1/CPE-mediated protection of these neurons against oxidative stress and glutamate neurotoxicity-induced cell death. Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB/BCL2 pathway to mediate stress-induced neuroprotection. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-04021-3.
- Published
- 2021
15. Neurodegeneration and astrogliosis in the entorhinal cortex in Alzheimer's disease: Stereological layer-specific assessment and proteomic analysis
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Veronica Astillero‐Lopez, Melania Gonzalez‐Rodriguez, Sandra Villar‐Conde, Alicia Flores‐Cuadrado, Alino Martinez‐Marcos, Isabel Ubeda‐Banon, and Daniel Saiz‐Sanchez
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Neurons ,Enfermedad de alzheimer ,Epidemiology ,Health Policy ,Stereology ,Estereología ,Proteomic ,Neuronas ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Proteómica ,Developmental Neuroscience ,Glia ,Corteza entorrinal ,Neurology (clinical) ,Geriatrics and Gerontology ,Alzheimer’s disease ,Entorhinal cortex - Abstract
Introduction: The entorhinal cortex is among the earliest areas involved in Alzheimer’s disease. Volume reduction and neural loss in this area have been widely reported. Human entorhinal cortex atrophy is, in part, due to neural loss, but microglial and/or astroglial involvement in the different layers remains unclear. Additionally, -omic approaches in the human entorhinal cortex are scarce. Methods: Herein, stereological layer-specific and proteomic analyses were carried out in the human brain. Results: Neurodegeneration, microglial reduction, and astrogliosis have been demonstrated, and proteomic data have revealed relationships with up- (S100A6, PPP1R1B, BAG3, and PRDX6) and downregulated (GSK3B, SYN1, DLG4, and RAB3A) proteins. Namely, clusters of these proteins were related to synaptic, neuroinflammatory, and oxidative stress processes. Discussion: Differential layer involvement among neural and glial populations determined by proteinopathies and identified proteins related to neurodegeneration and astrogliosis could explain how the cortical circuitry facilitates pathological spreading within the medial temporal lobe., Introducción La corteza entorrinal se encuentra entre las primeras áreas involucradas en la enfermedad de Alzheimer. La reducción de volumen y la pérdida neural en esta área han sido ampliamente reportadas. La atrofia de la corteza entorrinal humana se debe, en parte, a la pérdida neural, pero la participación microglial y/o astroglial en las diferentes capas sigue sin estar clara. Además, los enfoques -ómicos en la corteza entorrinal humana son escasos. Métodos En este documento, se llevaron a cabo análisis proteómicos y específicos de capa estereológica en el cerebro humano. Resultados Se ha demostrado la neurodegeneración, la reducción microglial y la astrogliosis, y los datos proteómicos han revelado relaciones con proteínas reguladas al alza (S100A6, PPP1R1B, BAG3 y PRDX6) y a la baja (GSK3B, SYN1, DLG4 y RAB3A). Es decir, los grupos de estas proteínas estaban relacionados con procesos de estrés oxidativo, neuroinflamatorio y sináptico. Discusión La participación de capas diferenciales entre poblaciones neurales y gliales determinada por proteinopatías y proteínas identificadas relacionadas con la neurodegeneración y la astrogliosis podría explicar cómo el circuito cortical facilita la propagación patológica dentro del lóbulo temporal medial.
- Published
- 2021
16. Somatostatin and Astroglial Involvement in the Human Limbic System in Alzheimer’s Disease
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Alino Martinez-Marcos, Melania Gonzalez-Rodriguez, Alicia Flores-Cuadrado, Sandra Villar-Conde, Daniel Saiz-Sanchez, Patricia Villanueva-Anguita, Isabel Ubeda-Bañon, Veronica Astillero-Lopez, and M Eugenia Paya-Rodriguez
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Adult ,Male ,QH301-705.5 ,hippocampus ,Tau protein ,Hippocampus ,Neuropeptide ,tau Proteins ,Biology ,somatostatin ,Catalysis ,Article ,Temporal lobe ,Inorganic Chemistry ,Limbic system ,Alzheimer Disease ,medicine ,Limbic System ,Humans ,Cognitive Dysfunction ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Aged ,Aged, 80 and over ,Amyloid beta-Peptides ,astroglia ,Organic Chemistry ,General Medicine ,Middle Aged ,Olfactory Bulb ,Computer Science Applications ,Olfactory bulb ,Chemistry ,medicine.anatomical_structure ,Somatostatin ,nervous system ,Astrocytes ,biology.protein ,stereology ,Cholinergic ,Female ,Neuroscience ,Alzheimer’s disease - Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly. Progressive accumulation of insoluble isoforms of amyloid-β peptide (Aβ) and tau protein are the major neuropathologic hallmarks, and the loss of cholinergic pathways underlies cognitive deficits in patients. Recently, glial involvement has gained interest regarding its effect on preservation and impairment of brain integrity. The limbic system, including temporal lobe regions and the olfactory bulb, is particularly affected in the early stages. In the early 1980s, the reduced expression of the somatostatin neuropeptide was described in AD. However, over the last three decades, research on somatostatin in Alzheimer’s disease has been scarce in humans. Therefore, the aim of this study was to stereologically quantify the expression of somatostatin in the human hippocampus and olfactory bulb and analyze its spatial distribution with respect to that of Aβ and au neuropathologic proteins and astroglia. The results indicate that somatostatin-expressing cells are reduced by 50% in the hippocampus but are preserved in the olfactory bulb. Interestingly, the coexpression of somatostatin with the Aβ peptide is very common but not with the tau protein. Finally, the coexpression of somatostatin with astrocytes is rare, although their spatial distribution is very similar. Altogether, we can conclude that somatostatin expression is highly reduced in the human hippocampus, but not the olfactory bulb, and may play a role in Alzheimer’s disease pathogenesis.
- Published
- 2021
17. The Human Hippocampus in Parkinson's Disease: An Integrative Stereological and Proteomic Study
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Alicia Flores-Cuadrado, Isabel Ubeda-Bañon, Veronica Astillero-Lopez, Melania Gonzalez-Rodriguez, Patricia Villanueva-Anguita, Alino Martinez-Marcos, Daniel Saiz-Sanchez, and Sandra Villar-Conde
- Subjects
0301 basic medicine ,Proteomics ,Research Report ,Parkinson's disease ,Synucleinopathies ,hippocampus ,Hippocampus ,neurons ,microglia ,Hippocampal formation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,alpha synuclein ,Humans ,human ,Cognitive decline ,Alpha-synuclein ,biology ,Neurodegeneration ,astrocytes ,Parkinson Disease ,medicine.disease ,Astrogliosis ,030104 developmental biology ,chemistry ,biology.protein ,alpha-Synuclein ,Neurology (clinical) ,NeuN ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Background: Parkinson’s disease (PD) is a prevalent neurodegenerative disease that is pathologically described as a six-stage α-synucleinopathy. In stage 4, α-synuclein reaches the hippocampus, inducing cognitive deficits, from which it progresses to the isocortex, leading to dementia. Among hippocampal fields, cornu ammonis 2 is particularly affected by this α-synucleinopathy and critical for cognitive decline. Volumetric studies using magnetic resonance imaging have produced controversial results, with only some reporting volume loss, whereas stereological data obtained using nonspecific markers do not reveal volume changes, neural or glial loss. Proteomic analysis has not been carried out in the hippocampus of patients with PD. Objective: This study aims to explain hippocampal changes in patients with PD at the cellular and proteomic levels. Methods: α-Synuclein inclusions, volume and neural (NeuN), microglial (Iba-1) and astroglial (GFAP) populations were stereologically analyzed. SWATH-MS quantitative proteomic analysis was also conducted. Results: Area fraction fractionator probe revealed a higher area fraction α-synucleinopathy in cornu ammonis 2. No volume change, neurodegeneration, microgliosis or astrogliosis was detected. Proteomic analysis identified 1,634 proteins, of which 83 were particularly useful for defining differences among PD and non-PD groups. Among them, upregulated (PHYIP, CTND2, AHSA1 and SNTA1) and downregulated (TM163, REEP2 and CSKI1) proteins were related to synaptic structures in the diseased hippocampus. Conclusion: The distribution of α-synuclein in the hippocampus is not associated with volumetric, neural or glial changes. Proteomic analysis, however, reveals a series of changes in proteins associated with synaptic structures, suggesting that hippocampal changes occur at the synapse level during PD.
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- 2021
18. What emotions do physical therapy students feel during their first visit to the dissection room?
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Carmen Romo-Barrientos, Daniel Torres Martín, Antonio Viñuela, María José Guzmán Pavón, Alicia Mohedano-Moriano, Isabel Ubeda-Bañon, Juan José Criado-Álvarez, Javier Aceituno-Gómez, Daniel Saiz-Sanchez, Miriam López Crespo, and Alino Martinez-Marcos
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Students, Medical ,education ,Anxiety ,Anxiety state ,03 medical and health sciences ,Surveys and Questionnaires ,medicine ,Cadaver ,Trait anxiety ,Humans ,Prosection ,Female students ,Physical Therapy Modalities ,Dissection ,General Medicine ,030104 developmental biology ,Cross-Sectional Studies ,Human anatomy ,Physical therapy ,Female ,030101 anatomy & morphology ,medicine.symptom ,Anatomy ,Psychology ,Developmental Biology - Abstract
Dissections are a fundamental practical methodology for teaching human anatomy. However, this experience can be stressful, generating anxiety situations among students. This study tries to understand the attitudes, reactions, fears and anxiety state among students earning a physiotherapy degree when facing their first prosection. A cross-sectional before-and-after study was carried out with students who were provided with an anonymous "ad hoc" questionnaire and the State-Trait Anxiety Inventory (STAI).The values obtained from the total STAI questionnaire remained stable and unchanged during the prosection (p0.05). The levels of trait anxiety (TA) and state anxiety (SA) remained stable except in female students, who showed higher TA and SA scores, with a significance of p0.05 before and after the prosection. Although 100% of the students were satisfied with the dissection practices, the experience can provoke stressful responses and should be addressed using coping mechanisms, especially among female students.
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- 2020
19. The human olfactory system in two proteinopathies: Alzheimer’s and Parkinson’s diseases
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Alicia Flores-Cuadrado, Juan Pablo Cabello-de la Rosa, Sandra Villar-Conde, Lucia Gonzalez-Lopez, Julia Vaamonde-Gamo, Daniel Saiz-Sanchez, Isabel Ubeda-Bañon, Fernanda Relea-Calatayud, Alicia Mohedano-Moriano, Veronica Astillero-Lopez, Alberto Rábano, Alino Martinez-Marcos, Ernesto Rioja-Corroto, Maria Jose Gallardo-Alcañiz, and Melania Gonzalez-Rodriguez
- Subjects
0301 basic medicine ,Olfactory system ,Nervous system ,Cognitive Neuroscience ,Tau protein ,Review ,Biology ,Anterior olfactory nucleus, hyposmia ,Amygdala ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Olfaction Disorders ,0302 clinical medicine ,Hyposmia ,Alzheimer Disease ,medicine ,Neuropil ,Humans ,Amyloid-β ,lcsh:Neurology. Diseases of the nervous system ,α-Synuclein ,Parkinson Disease ,Olfactory Pathways ,Entorhinal cortex ,Olfactory Bulb ,Anterior olfactory nucleus ,Smell ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Neurology (clinical) ,medicine.symptom ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders. Their etiologies are idiopathic, and treatments are symptomatic and orientated towards cognitive or motor deficits. Neuropathologically, both are proteinopathies with pathological aggregates (plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease, and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease). These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages. Both disorders present a long prodromal period, characterized by preclinical signs including hyposmia. Interestingly, the olfactory system, particularly the anterior olfactory nucleus, is initially and preferentially affected by the pathology. Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes. It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding (seeding), which then propagates through neurons and glia (spreading). Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading. Connectomic approaches reveal a number of hubs in the olfactory system (anterior olfactory nucleus, olfactory entorhinal cortex and cortical amygdala) that are key interconnectors with the main hubs (the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus) of network dysfunction in Alzheimer’s and Parkinson’s diseases.
- Published
- 2020
20. Somatostatin, Olfaction, and Neurodegeneration
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Melania Gonzalez-Rodriguez, Daniel Saiz-Sanchez, Alicia Flores-Cuadrado, Sandra Villar-Conde, Alino Martinez-Marcos, Veronica Astillero-Lopez, and Isabel Ubeda-Bañon
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0301 basic medicine ,Olfactory system ,Mini Review ,Neuropeptide ,Olfaction ,Biology ,amyloid-β ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,α-synuclein ,Hyposmia ,medicine ,tau ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,General Neuroscience ,hyposmia ,Neurodegeneration ,medicine.disease ,Anterior olfactory nucleus ,030104 developmental biology ,Somatostatin ,GABAergic ,anterior olfactory nucleus ,medicine.symptom ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders in aging. Hyposmia has been described as an early symptom that can precede cognitive and motor deficits by decades. Certain regions within the olfactory system, such as the anterior olfactory nucleus, display the neuropathological markers tau and amyloid-β or α-synuclein from the earliest stages of disease progression in a preferential manner. Specific neuronal subpopulations, namely those expressing somatostatin (SST), are preferentially affected throughout the olfactory and limbic systems. SST is a neuropeptide present in a subpopulation of GABAergic interneurons throughout the brain and its main function is to inhibit principal neurons and/or other interneurons. It has been reported that SST expression is reduced by 50% in Alzheimer's disease and that it is related to the formation of Aβ oligomers. The mechanisms underlying the preferential vulnerability of SST-expressing neurons in Alzheimer's disease (and, to a minor extent, in Parkinson's disease) are not known but analysis of the available data could shed light on their etiology. This short review aims to update the knowledge of functional features of somatostatin within the olfactory system and its role in olfactory deficits during neurodegeneration.
- Published
- 2020
21. Anxiety among Medical Students when Faced with the Practice of Anatomical Dissection
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Jaime González-González, Juan José Criado-Álvarez, Carmen Romo Barrientos, Daniel Saiz-Sanchez, Antonio Viñuela, Alicia Mohedano-Moriano, José Luis Martín-Conty, Alino Martinez-Marcos, Isabel Ubeda-Bañon, and Alicia Flores-Cuadrado
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Adult ,Male ,0301 basic medicine ,Embryology ,Students, Medical ,Histology ,Psychometrics ,020205 medical informatics ,media_common.quotation_subject ,education ,Theoretical models ,02 engineering and technology ,Anxiety ,Young Adult ,03 medical and health sciences ,Surveys and Questionnaires ,Cadaver ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Humans ,Anatomical dissection ,Schools, Medical ,media_common ,Dissection ,General Medicine ,Feeling ,Female ,Attitude change ,030101 anatomy & morphology ,Anatomy ,medicine.symptom ,Descriptive research ,Psychology ,Educational program ,Education, Medical, Undergraduate ,Clinical psychology - Abstract
Practical training in the dissection of human cadavers is a fundamental and traditional component of human anatomy education in medical schools. This practice, however, can be stressful for students and can generate a certain amount of anxiety. The aim of this study is to explore the attitudes, reactions, and anxiety levels of first-year medical students when working in the dissecting room, over a period of one year, and to relate these anxiety levels to the results of our educational program. This is a before and after descriptive study of students at the University of Castilla-La-Mancha. Questionnaires were distributed among them before and after their dissection practices in order to understand their feelings and emotions and their satisfaction about this activity. State-Trait Anxiety Inventory questionnaires were used to assess the students' 'state anxiety' (SA), which dropped significantly from 49.1% to 14% by the end of their first year. Female students started with higher levels of SA than their male counterparts but by the end of the year these had dropped to similar levels. Anxiety and fearful thoughts tended to drop (P > 0.05). In contrast, uncertainty levels showed significant changes, falling from 44.4% to 12.3%. Nonetheless, 100% of students would go through the experience again. Indeed, 98.2% considered that dissection practices were useful in reinforcing the theoretical aspects of their education, and 80.7% believed that dissecting was more useful than theoretical models. Although students were satisfied with dissection practices the experience cause stressful responses.
- Published
- 2018
22. Cranial Pair 0: The Nervus Terminalis
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Patricia Villanueva-Anguita, Maria Jose Gallardo-Alcañiz, Lucia Gonzalez-Lopez, Daniel Saiz-Sanchez, Ángel Peña-Melián, Alicia Flores-Cuadrado, Julia Vaamonde-Gamo, Alino Martinez-Marcos, Fernanda Relea-Calatayud, and Juan Pablo Cabello-de la Rosa
- Subjects
0301 basic medicine ,Nasal cavity ,Histology ,Cerebrum ,Neural crest ,Hippocampus ,Ethmoid bone ,Anatomy ,Biology ,Olfactory trigone ,Ganglion ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,medicine ,Crista galli ,030217 neurology & neurosurgery ,Ecology, Evolution, Behavior and Systematics ,Biotechnology - Abstract
Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Developmentally, the nervus terminalis is clearly observed in human embryos; subsequently, during the fetal period loses some of its ganglion cells, and it is less recognizable in adults. Fibers originating in the nasal cavity passes into the cranium through the middle area of the cribiform plate of the ethmoid bone. Intracranially, fibers joint the telencephalon at several sites including the olfactory trigone and the primordium of the hippocampus to reach preoptic and precommissural regions. The nervus terminalis shows ganglion cells, that sometimes form clusters, normally one or two located at the base of the crista galli, the so-called ganglion of the nervus terminalis. Its function is uncertain. It has been described that its fibers facilitates migration of luteinizing hormone-releasing hormone cells to the hypothalamus thus participating in the development of the hypothalamic-gonadal axis, which alteration may provoke Kallmann's syndrome in humans. This review summarizes current knowledge on this structure, incorporating original illustrations of the nerve at different developmental stages, and focuses on its anatomical and clinical relevance. Anat Rec, 302:394-404, 2019. © 2018 Wiley Periodicals, Inc.
- Published
- 2018
23. Learning from human cadaveric prosections: Examining anxiety in speech therapy students
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Alino Martinez-Marcos, Jaime González González, Alicia Flores-Cuadrado, Alicia Mohedano-Moriano, Daniel Saiz-Sanchez, Carmen Romo Barrientos, Isabel Ubeda-Bañon, Juan José Criado-Álvarez, and Juan Carlos Albertos-Marco
- Subjects
0301 basic medicine ,Embryology ,Histology ,media_common.quotation_subject ,education ,General Medicine ,Likert scale ,03 medical and health sciences ,Dissection ,Feeling ,medicine ,Anxiety ,030101 anatomy & morphology ,Anatomy ,Prosection ,medicine.symptom ,Cadaveric spasm ,Psychology ,Association (psychology) ,Clinical psychology ,Biomedical sciences ,media_common - Abstract
Human anatomy education often utilizes the essential practices of cadaver dissection and examination of prosected specimens. However, these exposures to human cadavers and confronting death can be stressful and anxiety-inducing for students. This study aims to understand the attitudes, reactions, fears, and states of anxiety that speech therapy students experience in the dissection room. To that end, a before-and-after cross-sectional analysis was conducted with speech therapy students undertaking a dissection course for the first time. An anonymous questionnaire was administered before and after the exercise to understand students' feelings and emotions. State-Trait Anxiety Inventory questionnaires (STAI-S and STAI-T) were used to evaluate anxiety levels. The results of the study revealed that baseline anxiety levels measured using the STAI-T remained stable and unchanged during the dissection room experience (P > 0.05). Levels of emotional anxiety measured using the STAI-S decreased, from 15.3 to 11.1 points (P 0.05). A total of 63.4% of students described having thoughts about life and death. After the session, 100% of students recommended the dissection exercise, giving it a mean score of 9.1/10 points. Anatomy is an important subject for students in the health sciences, and dissection and prosection exercises frequently involve a series of uncomfortable and stressful experiences. Experiences in the dissection room may challenge some students' emotional equilibria. However, students consider the exercise to be very useful in their education and recommend it. Anat Sci Educ 10: 487-494. © 2017 American Association of Anatomists.
- Published
- 2017
24. Anxiety among nursing students during their first human prosection
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Alberto Martínez-Lorca, Alicia Flores-Cuadrado, José Luis Martín-Conty, Daniel Saiz-Sanchez, Carmen Romo-Barrientos, Isabel Ubeda-Bañon, Antonio Viñuela, Juan José Criado-Álvarez, Alicia Mohedano-Moriano, Beatriz Rodríguez-Martín, and Alino Martinez-Marcos
- Subjects
Male ,Adolescent ,Psychometrics ,Universities ,media_common.quotation_subject ,Anxiety ,Education ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Nursing ,Surveys and Questionnaires ,Adaptation, Psychological ,medicine ,Trait anxiety ,Humans ,030212 general & internal medicine ,Nurse education ,Prosection ,General Nursing ,media_common ,030504 nursing ,Dissection ,Education, Nursing, Baccalaureate ,Anatomy education ,Feeling ,Spain ,Female ,Students, Nursing ,medicine.symptom ,0305 other medical science ,Psychology ,Biomedical sciences - Abstract
Dissection and prosection practices using human cadavers are a key component of macroscopic anatomy education in different Health Sciences university degrees. However, first-hand interaction with cadavers can be distressing for students, generating anxiety on a number of levels. This study aims to shed light on the reactions, fears and different states of anxiety experienced by nursing students in to a single anatomy room experience over a five-hour period, and examined reactions pre and post same. A descriptive study of these students was designed in order to understand their feelings and emotions, based on the distribution of anonymous "ad hoc" questionnaires before and after the practices. Also, State-Trait Anxiety Inventory (STAI) questionnaires were administered in order to assess their anxiety levels: Trait Anxiety (TA), which measures basal anxiety levels, and State Anxiety (SA), which measures individual emotional responses during a specific event (in this case, the prosection practice). The results of this study indicate that basal anxiety levels, measured as TA, remained stable and unchanged during the practice (p 0.05). SA or emotional anxiety levels, on the other hand, dropped from 21.3 to 17.8 points (p 0.05). Before the start of the practical exercise, 17.6% of the students admitted experiencing some kind of anxiety. Afterwards, however, 90.2% of the students said they would recommend these practices. They considered that prosection practices very useful for their education and recommended that they be retained for future courses. However, our study also showed the relevance of using coping mechanisms before the first contact with the dissecting room, especially for those students who did not feel emotionally prepared for it beforehand.
- Published
- 2019
25. Human ß-amyloid enriched extracts: evaluation of in vitro and in vivo internalization and molecular characterization
- Author
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Margarita Villar, Alino Martinez-Marcos, Lourdes Mateos-Hernández, Cristina M. Pedrero-Prieto, Mario Durán-Prado, José de la Fuente, Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Juan R. Peinado, Daniel Saiz-Sanchez, Francisco J. Alcaín, Javier Frontiñán-Rubio, Ministerio de Economía y Competitividad (España), Junta de Comunidades de Castilla-La Mancha, European Commission, Department of Medical Sciences, Oxidative Stress and Neurodegeneration Group, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM)-Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Neuroplasticity and Neurodegeneration Group, SaBio, IREC (CSIC-UCLM-JCCM), Instituto de Investigación en Recursos Cinegéticos (IREC), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University [Stillwater] (OSU)-Oklahoma State University [Stillwater] (OSU), Spanish Ministry of Economy and Competitiveness-FEDER SAF2016-75768-RMINECO-RETOS (AEI-FEDER) European Union (EU) SBPLY/17/180501/000430, University of Castilla-La Mancha (UCLM)-University of Castilla-La Mancha (UCLM), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Oklahoma State University [Stillwater]-Oklahoma State University [Stillwater]
- Subjects
0301 basic medicine ,Olfactory system ,Proteomics ,Cell ,Protein aggregation ,Hippocampus ,lcsh:RC346-429 ,Mice ,0302 clinical medicine ,Amyloid- internalization ,Internalization ,Cells, Cultured ,media_common ,Microglia ,Chemistry ,Alzheimer's disease ,Amygdala ,3. Good health ,Olfactory Cortex ,medicine.anatomical_structure ,Neurology ,Biochemistry ,Female ,Alzheimer’s disease ,Prions ,Cognitive Neuroscience ,media_common.quotation_subject ,Tissue Banks ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Amyloid-β internalization ,Amyloid ,lcsh:RC321-571 ,03 medical and health sciences ,Alzheimer Disease ,In vivo ,medicine ,Prion-like hypothesis ,Animals ,Humans ,Amyloid-β ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,lcsh:Neurology. Diseases of the nervous system ,Amyloid beta-Peptides ,Research ,Endothelial Cells ,Peptide Fragments ,In vitro ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Microvessels ,Neurology (clinical) ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
[Background]: Intracerebral inoculation of extracts from post-mortem human Alzheimer’s disease brains into mice produces a prion-like spreading effect of amyloid-β. The differences observed between these extracts and the synthetic peptide, in terms of amyloid-β internalization and seed and cell-to-cell transmission of cytosolic protein aggregates, suggest that brain extracts contain key contributors that enhance the prion-like effect of amyloid-β. Nevertheless, these potential partners are still unknown due to the complexity of whole brain extracts., [Methods]: Herein, we established a method based on sequential detergent solubilization of post-mortem samples of human brains affected by Alzheimer’s disease that strongly enrich amyloid-β aggregates by eliminating 92% of the remaining proteins. Internalization of Aβ1–42 from the enriched AD extracts was evaluated in vitro, and internalization of fluorescent-labeled AD extracts was also investigated in vivo. Furthermore, we carried out a molecular characterization of the Aβ-enriched fraction using label-free proteomics, studying the distribution of representative components in the amygdala and the olfactory cortex of additional human AD brain samples by immunohistochemistry., [Results]: Aβ1–42 from the enriched AD extracts are internalized into endothelial cells in vitro after 48 h. Furthermore, accumulation of fluorescent-labeled Aβ-enriched extracts into mouse microglia was observed in vivo after 4 months of intracerebral inoculation. Label-free proteomics (FDR < 0.01) characterization of the amyloid-β-enriched fraction from different post-mortem samples allowed for the identification of more than 130 proteins, several of which were significantly overrepresented (i.e., ANXA5 and HIST1H2BK; p < 0.05) and underrepresented (i.e., COL6A or FN1; p < 0.05) in the samples with Alzheimer’s disease. We were also able to identify proteins exclusively observed in Alzheimer’s disease (i.e., RNF213) or only detected in samples not affected by the disease (i.e., CNTN1) after the enrichment process. Immunohistochemistry against these proteins in additional tissues revealed their particular distribution in the amygdala and the olfactory cortex in relation to the amyloid-β plaque., [Conclusions]: Identification and characterization of the unique features of these extracts, in terms of amyloid-β enrichment, identification of the components, in vitro and in vivo cell internalization, and tissue distribution, constitute the best initial tool to further investigate the seeding and transmissibility proposed in the prion-like hypothesis of Alzheimer’s disease., Sponsored by the Spanish Ministry of Economy and Competitiveness-FEDER (grant # SAF2016-75768-R) to AMM, MINECO-RETOS (AEI-FEDER) to MDP, and the Autonomous Government of Castilla-La Mancha/FEDER (grant no. SBPLY/ 17/180501/000430) to AMM and DSS.
- Published
- 2019
26. Loss of One Engrailed1 Allele Enhances Induced α-Synucleinopathy
- Author
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Katelyn Becker, Sonia George, Daniel Saiz Sanchez, Patrik Brundin, Jeffrey H. Kordower, Diptaman Chatterjee, Jennifer A. Steiner, Nolwen L. Rey, Jiyan Ma, Martha L. Escobar Galvis, Zachary Madaj, and Emmanuel Quansah
- Subjects
0301 basic medicine ,Research Report ,engrailed ,Parkinson's disease ,Synucleinopathies ,Stereology ,Striatum ,Mice ,0302 clinical medicine ,Stereotactic injections ,propagation ,proteinopathy ,PD pathology ,α-Synuclein ,Cerebral Cortex ,0303 health sciences ,Neurodegeneration ,neurodegeneration ,Brain ,Parkinson Disease ,Amygdala ,Immunohistochemistry ,Pathophysiology ,3. Good health ,Ventral tegmental area ,Substantia Nigra ,medicine.anatomical_structure ,Nigral neuron degeneration ,Enfermedad de Parkinson ,Gene Knockdown Techniques ,alpha-Synuclein ,medicine.medical_specialty ,Substantia nigra ,pS129 α-synuclein scoring ,Neuropathology ,Biology ,Protein Aggregation, Pathological ,Cellular and Molecular Neuroscience ,03 medical and health sciences ,Protein Aggregates ,Internal medicine ,medicine ,Animals ,Humans ,mouse models ,030304 developmental biology ,Homeodomain Proteins ,Euthanasia ,Misfolded α-synuclein ,Ventral Tegmental Area ,misfolded proteins ,medicine.disease ,Neostriatum ,030104 developmental biology ,Endocrinology ,nervous system ,Complex I impairment ,Injection of PFFs ,Parkinson’s disease ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Parkinson’s disease (PD) is a synucleinopathy that has multiple neuropathological characteristics, with nigrostriatal dopamine system degeneration being a core feature. Current models of PD pathology typically fail to recapitulate several attributes of the pathogenic process and neuropathology. We aimed to define the effects of combining a mouse model exhibiting multiple PD-like changes with intrastriatal injections of α-synuclein (α-syn) pre-formed fibril (PFFs) aggregates. We employed the heterozygous Engrailed 1 (En1+/–) mouse that features several pathophysiological hallmarks of clinical PD., La enfermedad de Parkinson (EP) es una sinucleinopatía que tiene múltiples características neuropatológicas, siendo la degeneración del sistema dopaminérgico nigroestriatal una característica central. Los modelos actuales de patología de la EP generalmente no logran recapitular varios atributos del proceso patogénico y la neuropatología. Nuestro objetivo fue definir los efectos de combinar un modelo de ratón que presentaba múltiples cambios similares a los de la EP con inyecciones intraestriatales de agregados de fibrillas preformadas (PFF) de α-sinucleína (α-syn). Empleamos el ratón heterocigoto Engrailed 1 (En1+/–) que presenta varias características fisiopatológicas de la EP clínica.
- Published
- 2019
27. Hippocampal α-synuclein and interneurons in Parkinson's disease: Data from human and mouse models
- Author
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Carlos de la Rosa-Prieto, Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, Alicia Flores-Cuadrado, and Alino Martinez-Marcos
- Subjects
0301 basic medicine ,Parkinson's disease ,biology ,Interneuron ,musculoskeletal, neural, and ocular physiology ,Dentate gyrus ,Hippocampus ,Hippocampal formation ,medicine.disease ,Calbindin ,nervous system diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,nervous system ,Neurology ,mental disorders ,biology.protein ,medicine ,Neurology (clinical) ,Calretinin ,Neuroscience ,030217 neurology & neurosurgery ,Parvalbumin - Abstract
Background Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients. Methods The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed. Results In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus. Conclusions The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society
- Published
- 2016
28. Extracellular interaction between Neurotrophic factor‐α1 and HTR1E serotonin receptor promotes cell survival
- Author
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William A. Goddard, Soo-Kyung Kim, Daniel-Saiz Sanchez, Y. Peng Loh, Vinay Kumar Sharma, and Yang Xuyu
- Subjects
Neurotrophic factors ,Chemistry ,Genetics ,Extracellular ,Molecular Biology ,Biochemistry ,5-HT receptor ,Cell survival ,Biotechnology ,Cell biology - Published
- 2020
29. Differential Effects of Parkinson's Disease on Interneuron Subtypes within the Human Anterior Olfactory Nucleus
- Author
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Alicia Flores-Cuadrado, Alino Martinez-Marcos, Daniel Saiz-Sanchez, and Isabel Ubeda-Bañon
- Subjects
0301 basic medicine ,Olfactory system ,Interneuron ,Neuroscience (miscellaneous) ,Olfaction ,Biology ,somatostatin ,Calbindin ,lcsh:RC321-571 ,lcsh:QM1-695 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Calcium-binding protein ,medicine ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,lcsh:Human anatomy ,calcium binding protein ,non-motor symptoms ,α-synucleinopathy ,Anterior olfactory nucleus ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,biology.protein ,Anatomy ,Calretinin ,Neuroscience ,030217 neurology & neurosurgery ,Parvalbumin ,olfaction - Abstract
Synucleinopathies (including α-synucleinopathies), which include Parkinson’s disease (PD), manifest themsevles early on (stage 1) in the olfactory system; preferentially in the anterior olfactory nucleus (AON). In particular, the non-motor, early manifestations of PD include hyposmia, which is the partial loss of the sense of smell. The neural basis of hyposmia in PD, however, is poorly understood; but the AON appears to be a key structure in the disease’s progression. We analyzed whether α-synuclein was involved in the differential interneuron vulnerability associated with PD in the retrobulbar, cortical anterior and cortical posterior divisions of the AON. First, we determined the expression of the calcium binding interneuron markers, calretinin, calbindin and parvalbumin, as well as non-calcium binding interneuron marker, somatostatin, in neuronal cell bodies alone (cells/mm2) and in neuronal cell bodies and neurites (% of area fraction) of post-mortem tissue from PD cases and age-matched controls (n = 4 for each) by immunofluorescent confocal microscopy. Results indicated that parvalbumin expression was upregulated in neuronal cell bodies throughout the anterior olfactory nucleus of PD cases compared with controls. Furthermore, there was increased calbindin, calretinin and parvalbumin expression in the cell bodies and neurites of neurons in the retrobulbar division and also increased parvalbumin expression in the neurites of neurons in the cortical division; calretinin expression was also increased in neuronal cell bodies and neurites in the cortical posterior division. Second, we analyzed the co-localization of the above markers with α-synuclein, with results indicating that α-synuclein co-localized with the calcium-binding proteins, but only partially with somatostatin. Taken together, these results indicate differential expression levels among different neural markers in the divisions of the AON in PD cases and point to several possibilities, among them: possible neuroprotective mechanisms of calcium-binding proteins against α-synuclein; and the differential involvement of somatostatin in α-synuclein-positive cell bodies and neurites.
- Published
- 2017
30. Learning from human cadaveric prosections: Examining anxiety in speech therapy students
- Author
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Juan Jose, Criado-Álvarez, Jaime, González González, Carmen, Romo Barrientos, Isabel, Ubeda-Bañon, Daniel, Saiz-Sanchez, Alicia, Flores-Cuadrado, Juan Carlos, Albertos-Marco, Alino, Martinez-Marcos, and Alicia, Mohedano-Moriano
- Subjects
Adult ,Male ,Students, Medical ,Dissection ,Anxiety ,Speech Therapy ,Young Adult ,Cross-Sectional Studies ,Attitude ,Surveys and Questionnaires ,Cadaver ,Humans ,Female ,Curriculum ,Anatomy ,Education, Medical, Undergraduate - Abstract
Human anatomy education often utilizes the essential practices of cadaver dissection and examination of prosected specimens. However, these exposures to human cadavers and confronting death can be stressful and anxiety-inducing for students. This study aims to understand the attitudes, reactions, fears, and states of anxiety that speech therapy students experience in the dissection room. To that end, a before-and-after cross-sectional analysis was conducted with speech therapy students undertaking a dissection course for the first time. An anonymous questionnaire was administered before and after the exercise to understand students' feelings and emotions. State-Trait Anxiety Inventory questionnaires (STAI-S and STAI-T) were used to evaluate anxiety levels. The results of the study revealed that baseline anxiety levels measured using the STAI-T remained stable and unchanged during the dissection room experience (P 0.05). Levels of emotional anxiety measured using the STAI-S decreased, from 15.3 to 11.1 points (P 0.05). In the initial phase of the study, before any contact with the dissection room environment, 17% of students experienced anxiety, and this rate remained unchanged by end of the session (P 0.05). A total of 63.4% of students described having thoughts about life and death. After the session, 100% of students recommended the dissection exercise, giving it a mean score of 9.1/10 points. Anatomy is an important subject for students in the health sciences, and dissection and prosection exercises frequently involve a series of uncomfortable and stressful experiences. Experiences in the dissection room may challenge some students' emotional equilibria. However, students consider the exercise to be very useful in their education and recommend it. Anat Sci Educ 10: 487-494. © 2017 American Association of Anatomists.
- Published
- 2016
31. Neurogenesis, neurodegeneration, interneuron vulnerability and amyloid-β in the olfactory bulb of APP/PS1 mouse model of Alzheimer’s disease
- Author
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Alicia Flores-Cuadrado, Alino Martinez-Marcos, Daniel Saiz-Sanchez, Carlos de la Rosa-Prieto, and Isabel Ubeda-Bañon
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Interneuron ,somatostatin ,Tau protein ,lcsh:RC321-571 ,03 medical and health sciences ,0302 clinical medicine ,calbindin ,Internal medicine ,mental disorders ,parvalbumin ,medicine ,Amyloid precursor protein ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,biology ,General Neuroscience ,calretinin ,Neurogenesis ,Neurodegeneration ,medicine.disease ,Granule cell ,Olfactory bulb ,adult neurogenesis ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,nervous system ,biology.protein ,NeuN ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Alzheimer´s disease is the most prevalent neurodegenerative disease, mostly idiopathic and with palliative treatment. Neuropathologically, it is characterized by intracellular neurofibrillary tangles of tau protein and extracellular plaques of amyloid β peptides. The relationship between Alzheimer’s disease and neurogenesis is unknown, but two facts are particularly relevant. First, early aggregation sites of both proteinopathies include the hippocampal formation and the olfactory bulb, which have been correlated to memory and olfactory deficits, respectively. These areas are well-recognized integration zones of newly-born neurons in the adult brain. Second, molecules, such as amyloid precursor protein and presenilin-1 are common to both Alzheimer’s disease etiology and neurogenic development. Adult neurogenesis in Alzheimer’s disease models has been studied in the hippocampus, but only occasionally addressed in the olfactory bulb and results are contradictory. To gain insight on the relationship between adult neurogenesis and Alzheimer’s disease, this work analyzes neurogenesis, neurodegeneration, interneuron vulnerability and amyloid-β involvement in the olfactory bulb of an Alzheimer’s disease model. Control and double-transgenic mice carrying the amyloid precursor protein and the presenilin-1 genes, which give rise amyloid β plaques have been used. BrdU-treated animals have been studied at 16, 30, 43 and 56 weeks of age. New-born cell survival (BrdU), neuronal loss (using neuronal markers NeuN and PGP9.5), differential interneuron (calbindin-, parvalbumin-, calretinin- and somatostatin-expressing populations) vulnerability and involvement by amyloid β have been analyzed. Neurogenesis increases with aging in the granule cell layer of control animals from 16 to 43 weeks. No neuronal loss has been observed after quantifying NeuN or PGP9.5. Regarding interneuron population vulnerability: calbindin-expressing neurons remains unchanged; parvalbumin-expressing neurons trend to increase with aging in transgenic animals; calretinin-expressing neurons increase with aging in transgenic mice and decrease in control animals and neurogenesis is higher in control as compared to transgenic animals at given ages, finally; somatostatin-expressing neurons of transgenic mice decrease with aging and as compared to controls. Amyloid β aggregates with aging in the granule cell layer, which may be related to the particular involvement of somatostatin-expressing cells.
- Published
- 2016
32. α-Synuclein in the olfactory system of a mouse model of Parkinson’s disease: correlation with olfactory projections
- Author
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Alino Martinez-Marcos, Daniel Saiz-Sanchez, Carlos de la Rosa-Prieto, and Isabel Ubeda-Bañon
- Subjects
Male ,Olfactory system ,Histology ,Mice, Transgenic ,Substantia nigra ,Biology ,Amygdala ,Mice ,Piriform cortex ,Neural Pathways ,medicine ,Animals ,Entorhinal Cortex ,General Neuroscience ,Olfactory tubercle ,Parkinson Disease ,Olfactory Pathways ,Entorhinal cortex ,Olfactory Bulb ,Olfactory bulb ,Anterior olfactory nucleus ,Disease Models, Animal ,medicine.anatomical_structure ,nervous system ,Mutation ,alpha-Synuclein ,Female ,Cell Surface Extensions ,Anatomy ,Neuroscience - Abstract
Olfactory deficits are an early feature of Parkinson's disease (PD). Neuropathologically, α-synucleinopathy (Lewy bodies and neurites) is observed earlier (stage 1) in the olfactory system than in the substantia nigra (stage 3), and this could underlies the early olfactory symptoms. In the present report, we analyzed the distribution of α-synuclein deposits in tertiary olfactory structures (anterior olfactory nucleus, olfactory tubercle, piriform cortex, posterolateral cortical amygdala and lateral entorhinal cortex) of homozygous transgenic mice (aged 2-8 months) overexpressing the human A53T variant of α-synuclein. To address the hypothesis of progressive α-synucleinopathy within the olfactory system, the distribution of α-synuclein was analyzed in conjunction with tracer injections into the main olfactory bulb. The time-course of α-synuclein expression revealed a significant increase in the piriform cortex at the age of 8 months compared to other brain structures. Tracing experiments revealed that olfactory projections are reduced in homozygous as compared to wild type animals. Double-labeling experiments show labeled axonal collaterals of mitral cells entering layer II of the piriform cortex in close proximity to α-synuclein-positive cells. To our knowledge, this is the first study addressing the progression of α-synuclein expression in a vulnerable neuronal pathway in PD.
- Published
- 2011
33. Maturation of newly born vomeronasal neurons in the adult mice
- Author
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Daniel Saiz-Sanchez, Alino Martinez-Marcos, Alicia Mohedano-Moriano, Isabel Ubeda-Bañon, and Carlos de la Rosa-Prieto
- Subjects
Male ,Vomeronasal organ ,Neurogenesis ,Cellular differentiation ,Fluorescent Antibody Technique ,Biology ,Developmental psychology ,Mice ,Neural Stem Cells ,Neuroblast ,Neural Pathways ,medicine ,Animals ,Receptor ,Neurons ,General Neuroscience ,Cell Differentiation ,Accessory Olfactory Bulb ,Olfactory Bulb ,Epithelium ,Cell biology ,medicine.anatomical_structure ,nervous system ,Apoptosis ,Female ,Vomeronasal Organ - Abstract
The olfactory and vomeronasal epithelia detect chemical stimuli in most tetrapods. Both epithelia undergo neural replacement during adulthood. In the central regions of vomeronasal epithelium, similar rates of neurogenesis and apoptosis evidence balanced replacement mechanisms. In the margins, the rate of neurogenesis is several times higher as compared with the rate of apoptosis suggesting net addition of neural receptor cells during adulthood. Herein, the fate of these marginal neuroblasts has been investigated in adult mice. Newly born and mature receptor neurons have been labeled. In the margins, more than 60% of new-born cells send axons to the accessory olfactory bulb. These results evidence that new neural elements from the vomeronasal epithelium are added to the accessory olfactory bulb preexisting circuitry.
- Published
- 2011
34. Neurogenesis in subclasses of vomeronasal sensory neurons in adult mice
- Author
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Alino Martinez-Marcos, Susana Garcia-Muñozguren, L. Argandoña-Palacios, C. de la Rosa-Prieto, Daniel Saiz-Sanchez, and Isabel Ubeda-Bañon
- Subjects
Male ,Sensory Receptor Cells ,Vomeronasal organ ,G protein ,Neurogenesis ,Fluorescent Antibody Technique ,Sensory system ,Biology ,Mice ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Developmental Neuroscience ,Animals ,Receptor ,Analysis of Variance ,Microscopy, Confocal ,Doublecortin ,Cell biology ,chemistry ,biology.protein ,Pheromone ,Female ,Vomeronasal Organ ,Neuroscience ,Bromodeoxyuridine - Abstract
The vomeronasal sensory epithelium contains two distinct populations of vomeronasal sensory neurons. Apical neurons express Gi2α-linked V1R vomeronasal receptors and project to the anterior portion of the accessory olfactory bulb, while basal neurons express Goα-linked V2R receptors and project to the posterior portion. Sensory neurons expressing V1R and V2R vomeronasal receptors are sensitive to different stimuli. Neurons in the vomeronasal system undergo continuous cell turnover during adulthood. To analyze over time neurogenesis of the different sensory cell populations, adult mice were injected with bromodeoxyuridine (BrdU) and sacrificed at postinjection days 1, 3, 5, 7, and 11. Newborn vomeronasal neurons were revealed by antibodies against BrdU while subclasses of vomeronasal neurons were identified using antibodies against Goα or Gi2α proteins. To ascertain whether G proteins are early expressed during neurogenesis, multiple labeling experiments using PSA-NCAM and doublecortin were performed. Distribution of BrdU-labeled cells was analyzed in angular segments from the margin of the sensory epithelium. No sexual differences were found. Within survival groups, BrdU-Goα labeled cells were found more marginally when compared with BrdU-Gi2α labeled cells. The number of BrdU-positive cells decreased from day 1 to day 3 to remain constant afterwards. The relative proportions of BrdU-Gi2α and BrdU-Goα labeled cells remained similar and constant from postinjection day 1 onwards. This rate was also comparable with BrdU-positive cells starting day 3. These results indicate an early, constant, and similar rate of neurogenesis in the two major subclasses of vomeronasal neurons, which suggests that both cell populations maturate independently. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 961–970, 2010
- Published
- 2010
35. Somatostatin, tau, and β-amyloid within the anterior olfactory nucleus in Alzheimer disease
- Author
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Daniel Saiz-Sanchez, Susana Garcia-Muñozguren, L. Argandoña-Palacios, Ricardo Insausti, Alino Martinez-Marcos, Isabel Ubeda-Bañon, and C. de la Rosa-Prieto
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Fluorescent Antibody Technique ,tau Proteins ,Olfaction ,Biology ,Olfaction Disorders ,Basal (phylogenetics) ,Developmental Neuroscience ,Alzheimer Disease ,β amyloid ,Internal medicine ,mental disorders ,medicine ,Humans ,Neprilysin ,Aged ,Aged, 80 and over ,Amyloid beta-Peptides ,Human brain ,Middle Aged ,medicine.disease ,Olfactory Bulb ,Anterior olfactory nucleus ,medicine.anatomical_structure ,Somatostatin ,Endocrinology ,Neurology ,Female ,Alzheimer's disease ,hormones, hormone substitutes, and hormone antagonists - Abstract
Impaired olfaction is an early symptom of Alzheimer disease (AD). This likely to reflect neurodegenerative processes taking place in basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus. Betaeta-amyloid (Abeta) accumulation in AD brain may relate to decline in somatostatin levels: somatostatin induces the expression of the Abeta-degrading enzyme neprilysin and somatostatin deficiency in AD may therefore reduce Abeta clearance. We have investigated the expression of somatostatin in the anterior olfactory nucleus of AD and control brain. We report that somatostatin levels were reduced by approximately 50% in AD brain. Furthermore, triple-immunofluorescence revealed co-localization of somatostatin expression with Abeta (65.43%) with Abeta and tau (19.75%) and with tau (2.47%). These data indicate that somatostatin decreases in AD and its expression may be linked with Abeta deposition.
- Published
- 2010
36. Fate of marginal neuroblasts in the vomeronasal epithelium of adult mice
- Author
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Susana Garcia-Muñozguren, Isabel Ubeda-Bañon, C. de la Rosa-Prieto, Alino Martinez-Marcos, Daniel Saiz-Sanchez, and L. Argandoña-Palacios
- Subjects
Male ,Vomeronasal organ ,Neurogenesis ,Cellular differentiation ,Apoptosis ,Sensory system ,Biology ,Mice ,Neuroblast ,Cell Movement ,medicine ,Animals ,Stem Cell Niche ,General Neuroscience ,Cell Differentiation ,Epithelial Cells ,Adult Stem Cells ,medicine.anatomical_structure ,nervous system ,biology.protein ,Female ,Basal lamina ,Vomeronasal Organ ,Stem cell ,Neuroscience ,Olfactory marker protein - Abstract
Chemical stimuli are sensed through the olfactory and vomeronasal epithelia, and the sensory cells of both systems undergo neuronal turnover during adulthood. In the vomeronasal epithelium, stem cells adjacent to the basal lamina divide and migrate to replace two classes of sensory neurons: apical neurons that express G(i2alpha)-linked V1R vomeronasal receptors and project to the anterior accessory olfactory bulb, and basal neurons that express G(oalpha)-linked V2R receptors and project to the posterior accessory olfactory bulb. Most of the dividing cells are present in the margins of the epithelium and only migrate locally. Previous studies have suggested that these marginal cells may participate in growth, sensory cell replacement or become apoptotic before maturation; however, the exact fate of these cells have remained unclear. In this work we investigated the fate of these marginal cells by analyzing markers of neurogenesis (bromodeoxyuridine incorporation), apoptosis (caspase-3), and neuronal maturation (olfactory marker protein and Neurotrace Nissl stain). Our data reveal a pool of dividing cells in the epithelial margins that predominantly give rise to mature neurons and only rarely undergo apoptosis. Newly generated cells are several times more numerous than apoptotic cells. These marginal neuroblasts could therefore constitute a net neural addition zone during adulthood.
- Published
- 2009
37. V1R and V2R segregated vomeronasal pathways to the hypothalamus
- Author
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Palma Pro-Sistiaga, Carlos de la Rosa-Prieto, Alicia Mohedano-Moriano, Alino Martinez-Marcos, Daniel Saiz-Sanchez, and Isabel Ubeda-Bañon
- Subjects
Male ,Olfactory system ,Receptors, Vasopressin ,Microinjections ,Vomeronasal organ ,Hypothalamus ,Biology ,Efferent Pathways ,Amygdala ,Rats, Sprague-Dawley ,Vomeronasal receptor ,medicine ,Animals ,Amines ,Fluorescent Dyes ,Afferent Pathways ,Rhodamines ,General Neuroscience ,Septal nuclei ,Dextrans ,Anatomy ,Olfactory Bulb ,Rats ,Olfactory bulb ,Stria terminalis ,medicine.anatomical_structure ,nervous system ,Pheromone ,Female ,Fluorescein ,Septal Nuclei ,Vomeronasal Organ ,Neuroscience - Abstract
The vomeronasal system is segregated from the epithelium to the bulb. Two classes of receptor neurons are apically and basally placed in the vomeronasal epithelium, express Gi2alpha and Goalpha proteins and V1R and V2R receptors and project to the anterior and posterior portions of the accessory olfactory bulb, respectively. Apart from common vomeronasal recipient structures in the amygdala, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala. The efferent projections from these two amygdaloid structures to the hypothalamus were investigated. These two vomeronasal subsystems mediated by V1R and V2R receptors were partially segregated, not only in amygdala, but also in the hypothalamus.
- Published
- 2008
38. Projections of olfactory bulbs to the olfactory and vomeronasal cortices
- Author
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Carlos de la Rosa-Prieto, Alicia Mohedano-Moriano, Daniel Saiz-Sanchez, Isabel Ubeda-Bañon, Alino Martinez-Marcos, and Palma Pro-Sistiaga
- Subjects
Male ,Olfactory system ,Microinjections ,Stilbamidines ,Vomeronasal organ ,Central nervous system ,Olfaction ,Biology ,Efferent Pathways ,Rats, Sprague-Dawley ,medicine ,Animals ,Fluorescent Dyes ,Cerebral Cortex ,Cerebrum ,General Neuroscience ,Olfactory tubercle ,Olfactory Pathways ,Anatomy ,Amygdala ,Olfactory Bulb ,Chemoreceptor Cells ,Rats ,Olfactory bulb ,medicine.anatomical_structure ,Microscopy, Fluorescence ,nervous system ,Female ,Neuroscience ,Olfactory epithelium - Abstract
Projections from the olfactory bulbs have been traditionally described as 'nontopographically organized'. Olfactory and vomeronasal projections have been reported to reach nonoverlapping cortical areas. Four receptor expression zones have been described in the olfactory epithelium, maintained in the main olfactory bulb, but none in the olfactory cortex. Recent data have demonstrated convergence in the basal telencephalon of olfactory and vomeronasal projections. Injections of methanesulfonate hydroxystilbamidine (FluoroGold) in the chemosensory cortex were done to map retrograde labeling in the bulbs. Topography was not observed in the four zones of the main olfactory bulb. Areas of the rostral telencephalon were shown to receive simultaneous inputs from the main and accessory olfactory bulbs.
- Published
- 2008
39. Hippocampal α-synuclein and interneurons in Parkinson's disease: Data from human and mouse models
- Author
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Alicia, Flores-Cuadrado, Isabel, Ubeda-Bañon, Daniel, Saiz-Sanchez, Carlos, de la Rosa-Prieto, and Alino, Martinez-Marcos
- Subjects
Disease Models, Animal ,Mice ,Interneurons ,alpha-Synuclein ,Animals ,Humans ,Mice, Transgenic ,Parkinson Disease ,Tissue Banks ,Hippocampus - Abstract
Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential α-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of α-synuclein in hippocampal interneurons in an α-synucleinopathy mouse model and in the brains of Parkinson's disease patients.The distribution of α-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with α-synuclein was analyzed.In mice, α-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of α-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The α-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus.The differential α-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. © 2016 International Parkinson and Movement Disorder Society.
- Published
- 2015
40. Interneurons in the human olfactory system in Alzheimer's disease
- Author
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Carlos de la Rosa-Prieto, Daniel Saiz-Sanchez, Alicia Flores-Cuadrado, Alino Martinez-Marcos, and Isabel Ubeda-Bañon
- Subjects
0301 basic medicine ,Olfactory system ,Pathology ,medicine.medical_specialty ,Interneuron ,Disease ,Biology ,Olfactory Receptor Neurons ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Alzheimer Disease ,Interneurons ,medicine ,Humans ,Olfactory memory ,Cholinergic neuron ,Pathological ,Neurodegeneration ,Olfactory Pathways ,medicine.disease ,Cholinergic Neurons ,Smell ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Alzheimer's disease ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.
- Published
- 2015
41. Olfactory and cortical projections to bulbar and hippocampal adult-born neurons
- Author
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Teresa Liberia, Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, Dulce Ma. Arzate, Alicia Flores-Cuadrado, Alino Martinez-Marcos, Carlos Crespo, Miguel de Moya-Pinilla, and Carlos de la Rosa-Prieto
- Subjects
hippocampus ,Rostral migratory stream ,Neuroscience (miscellaneous) ,Olfaction ,Biology ,lcsh:RC321-571 ,lcsh:QM1-695 ,Subgranular zone ,memory ,Cellular and Molecular Neuroscience ,synapse ,medicine ,Original Research Article ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,tract-tracing ,Dentate gyrus ,Olfactory tubercle ,lcsh:Human anatomy ,Granule cell ,Anterior olfactory nucleus ,Olfactory bulb ,adult neurogenesis ,medicine.anatomical_structure ,nervous system ,Anatomy ,Neuroscience ,olfaction - Abstract
New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto twenty-one-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.
- Published
- 2015
42. α-Synuclein staging in the amygdala of a Parkinson's disease model: cell types involved
- Author
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Alicia Flores-Cuadrado, Daniel Saiz-Sanchez, Alino Martinez-Marcos, Carlos de la Rosa-Prieto, and Isabel Ubeda-Bañon
- Subjects
Male ,medicine.medical_specialty ,Aging ,Calbindins ,Parkinson's disease ,Interneuron ,Substantia nigra ,Mice, Transgenic ,Biology ,Amygdala ,Calbindin ,Severity of Illness Index ,Parkinsonian Disorders ,Interneurons ,Calcium-binding protein ,Internal medicine ,mental disorders ,medicine ,Animals ,Microscopy, Confocal ,General Neuroscience ,medicine.disease ,Immunohistochemistry ,nervous system diseases ,Endocrinology ,Somatostatin ,medicine.anatomical_structure ,nervous system ,Calbindin 2 ,Disease Progression ,alpha-Synuclein ,Female ,Calretinin - Abstract
Lewy bodies (ubiquitin and α-synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non-motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α-synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co-localisation of these markers with α-synuclein was performed. Triple labeling of calbindin, somatostatin and α-synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α-Synuclein-positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non-significant increase over time from 16 to 30-43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α-Synuclein mostly co-localised with calbindin and a number of these cells also co-expressed somatostatin. These data on α-synucleinopathy staging in the amygdala could help to explain non-motor symptoms as well as to understand the progression of Parkinson's disease in the brain.
- Published
- 2014
43. α-Synuclein in the olfactory system in Parkinson’s disease: role of neural connections on spreading pathology
- Author
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Daniel Saiz-Sanchez, Alino Martinez-Marcos, Isabel Ubeda-Bañon, and Carlos de la Rosa-Prieto
- Subjects
Olfactory system ,medicine.medical_specialty ,Pathology ,Histology ,Neurology ,Parkinson's disease ,Lewy body ,General Neuroscience ,Parkinson Disease ,Substantia nigra ,Olfactory Pathways ,medicine.disease ,Olfactory Bulb ,Olfactory bulb ,Anterior olfactory nucleus ,nervous system ,alpha-Synuclein ,medicine ,Animals ,Humans ,Brainstem ,Anatomy ,Psychology ,Neuroscience - Abstract
Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, resting tremor, and postural instability. Neuropathologically, intracellular aggregates of α-synuclein in Lewy bodies and Lewy neurites appear in particular brain areas according to a sequence of stages. Clinical diagnosis is usually established when motor symptoms are evident (corresponding to Braak stage III or later), years or even decades after onset of the disease. Research at early stages is therefore essential to understand the etiology of PD and improve treatment. Although classically considered as a motor disease, non-motor symptoms have recently gained interest. Olfactory deficits are among the earliest non-motor features of PD. Interestingly, α-synuclein deposits are present in the olfactory bulb and anterior olfactory nucleus at Braak stage I. Several lines of evidence have led to proposals that PD pathology spreads by a prion-like mechanism via the olfactory and vagal systems to the substantia nigra. In this context, current data on the temporal appearance of α-synuclein aggregates in the olfactory system of both humans and transgenic mice are of particular relevance. In addition to the proposed retrograde nigral involvement via brainstem nuclei, olfactory pathways could potentially reach the substantia nigra, and the possibility of centrifugal progression warrants investigation. This review analyzes the involvement of α-synuclein in different elements of the olfactory system, in both humans and transgenic models, from the hodological perspective of possible anterograde and/or retrograde progression of this proteinopathy within the olfactory system and beyond-to the substantia nigra and the remainder of the central and peripheral nervous systems.
- Published
- 2013
44. Interneurons, tau and amyloid-β in the piriform cortex in Alzheimer's disease
- Author
-
Alino Martinez-Marcos, Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, and Carlos de la Rosa-Prieto
- Subjects
Olfactory system ,Male ,Histology ,Hippocampus ,Cell Count ,Piriform Cortex ,tau Proteins ,Olfaction ,Biology ,Alzheimer Disease ,Interneurons ,Piriform cortex ,Humans ,Olfactory memory ,Aged ,Aged, 80 and over ,Amyloid beta-Peptides ,General Neuroscience ,Middle Aged ,Entorhinal cortex ,Anterior olfactory nucleus ,Olfactory bulb ,Parvalbumins ,nervous system ,Calbindin 2 ,Female ,Anatomy ,Somatostatin ,Neuroscience - Abstract
Impaired olfaction has been described as an early symptom of Alzheimer's disease. Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Interestingly, neuropathology begins in the transentorhinal cortex and extends to the neighboring limbic system and basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus and olfactory bulb. The human piriform cortex has been described as a crucial area in odor quality coding; disruption of this region mediates early olfactory deficits in Alzheimer's disease. Most neuropathological investigations have focused on the entorhinal cortex and hippocampus, whereas the piriform cortex has largely been neglected. This work aims to characterize the expression of the neuropathological amyloid-β peptide, tau protein and interneuron population markers (calretinin, parvalbumin and somatostatin) in the piriform cortex of ten Alzheimer-diagnosed (80.4 ± 8.3 years old) and five control (69.6 ± 11.1) cases. Here, we examined the distribution of different interneuronal markers as well as co-localization of interneurons and pathological markers. Results indicated preferential vulnerability of somatostatin- (p = 0.0001 < α = 0.05) and calretinin-positive (p = 0.013 < α = 0.05) cells that colocalized with amyloid-β peptide, while the prevalence of parvalbumin-positive cells was increased (p = 0.045 < α = 0.05) in the Alzheimer's cases. These data may help to reveal the neural basis of olfactory deficits linked to Alzheimer's disease as well as to characterize neuronal populations preferentially vulnerable to neuropathology in regions critically involved in early stages of the disease.
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- 2013
45. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease
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Daniel, Saiz-Sanchez, Carlos, De La Rosa-Prieto, Isabel, Ubeda-Bañon, and Alino, Martinez-Marcos
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Amyloid beta-Peptides ,Time Factors ,Homozygote ,Age Factors ,Mice, Transgenic ,Olfactory Pathways ,Olfactory Bulb ,Smell ,Amyloid beta-Protein Precursor ,Disease Models, Animal ,Mice ,Parvalbumins ,Alzheimer Disease ,Interneurons ,Calbindin 2 ,Disease Progression ,Presenilin-1 ,Animals ,Humans ,Female ,Somatostatin - Abstract
Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta-amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder.
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- 2013
46. Neural Basis of Hyposmia in Alzheimer’s Disease
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Carlos de la Rosa-Prieto, Alino Martinez-Marcos, Daniel Saiz-Sanchez, and Isabel Ubeda-Bañon
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Olfactory system ,biology ,business.industry ,Tau protein ,Anosmia ,medicine.disease ,Limbic system ,medicine.anatomical_structure ,Hyposmia ,medicine ,biology.protein ,Dementia ,Senile plaques ,medicine.symptom ,business ,Neuroscience ,Olfactory epithelium - Abstract
At the beginning of twenty century Alois Alzheimer described the pathology that now bears his name (Alzheimer, 1907). Over a hundred years later, Alzheimer’s disease (AD) is the most common cause of dementia in developed countries. Here eighteen million people are currently affected and the number of patients is expected to increase dramatically with the ongoing increase in the elderly population (Fotuhi et al., 2009, Mount & Downton, 2006). Because no suitable biomarkers are available, the diagnosis of AD remains inconclusive until postmortem pathological analysis, and physicians rely on behavioral manifestations to differentiate between AD and other conditions. For this reason firm diagnosis is generally only made at later stages of the disorder when treatment is purely palliative. These features make AD a social and economic challenge in developed countries (Wimo et al., 2010). Clinically, AD is characterized by progressive loss of cognitive functions with specific deficits in episodic memory. Clinical diagnosis of is generally only made when cognitive deficits are sufficiently severe to cause dependent status of the patient (Nestor et al., 2004). Pathological analyses of AD brain have described two distinct types of proteinopathy in the frontal and temporal lobes involving the limbic system and the basal forebrain. The first type comprises aggregates of beta-amyloid peptide (Aβ) – a specific fragment of the amyloid precursor protein (APP), a plasma membrane protein. These aggregates accumulate in the extracellular space and give rise to senile plaques (SPs). SPs cause synaptotoxicity, neurotoxicity, oxidative stress and hypoxia (Peers et al., 2009, Selkoe, 2001, 2008). The second proteinopathy occurs in the cytosol. Hyperphosphorylation and abnormal aggregation of the microtubule-associated protein tau leads to the intracellular formation of neurofibrillary tangles (NFTs) which cause cytoskeleton destabilization and eventually cell death (Hernandez & Avila, 2008, Selkoe, 2001). It has been widely reported that olfactory loss (anosmia and hyposmia) takes place in the early stages of AD, and before any detectable cognitive deficits are present. Interestingly, AD pathology extends throughout the limbic system and the basal forebrain, including the olfactory system (Braak & Braak, 1991). The human olfactory system includes peripheral sensory neurons in the olfactory epithelium; these send their axons across the cribriform plate of the etmoides bone to the olfactory bulbs. In the glomerular layer of the olfactory
- Published
- 2011
47. Cladistic Analysis of Olfactory and Vomeronasal Systems
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Enrique Lanuza, Palma Pro-Sistiaga, Daniel Saiz-Sanchez, Alino Martinez-Marcos, Carlos de la Rosa-Prieto, Alicia Mohedano-Moriano, Isabel Ubeda-Bañon, Fernando Martínez-García, and Nicolas Gutierrez-Castellanos
- Subjects
Olfactory system ,Vomeronasal organ ,Neuroscience (miscellaneous) ,Sensory system ,Review Article ,Olfaction ,vomeronasal ,Biology ,lcsh:RC321-571 ,lcsh:QM1-695 ,Cellular and Molecular Neuroscience ,evolution ,medicine ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Cerebrum ,lcsh:Human anatomy ,amygdala ,Amygdala ,Olfactory Bulb ,Olfactory bulb ,medicine.anatomical_structure ,cortex ,olfactory bulb ,Cortex ,Pheromone ,Anatomy ,Neuroscience ,Olfactory tract ,olfaction - Abstract
Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.
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- 2011
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48. Staging of alpha-synuclein in the olfactory bulb in a model of Parkinson's disease: cell types involved
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Soledad Calvo, Alicia Mohedano-Moriano, L. Argandoña-Palacios, Carlos de la Rosa-Prieto, Noelia Fradejas, Susana Garcia-Muñozguren, Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, and Alino Martinez-Marcos
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Olfactory system ,Cell type ,Pathology ,medicine.medical_specialty ,Parkinson's disease ,Tyrosine 3-Monooxygenase ,Central nervous system ,Substantia nigra ,Mice, Transgenic ,Olfaction ,Neuropathology ,Mice ,mental disorders ,medicine ,Animals ,Humans ,Ubiquitins ,Neurons ,Parkinson Disease ,medicine.disease ,Olfactory Bulb ,nervous system diseases ,Olfactory bulb ,Disease Models, Animal ,medicine.anatomical_structure ,Parvalbumins ,nervous system ,Neurology ,Gene Expression Regulation ,Mutation ,alpha-Synuclein ,Neurology (clinical) ,Psychology ,Neuroscience - Abstract
Impaired olfaction is an early symptom of Parkinson's disease. The underlying neuropathology likely includes alpha-synucleinopathy in the olfactory bulb at an earlier stage (Braak's stage1) than pathology in the substantia nigra, which is not observed until stage 3. In this report, we investigated the distribution and cell types affected by alpha-synuclein in the olfactory bulb of transgenic mice (2-8 months of age) expressing the human A53T variant of alpha-synuclein. alpha-Synuclein immunostaining progressively affects interneurons and mitral cells. Double labeling studies demonstrate that dopaminergic cells are hardly involved, whereas glutamatergic- and calcium binding protein-positive cells are severely affected. This temporal evolution and the cell types expressing alpha-synuclein are reminiscent of idiopathic Parkinson's disease and support the usefulness of this model to address specific topics in the premotor phase of the disease.
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- 2010
49. alpha-Synucleinopathy in the human olfactory system in Parkinson's disease: involvement of calcium-binding protein- and substance P-positive cells
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Daniel Saiz-Sanchez, L. Argandoña-Palacios, Alino Martinez-Marcos, Carlos de la Rosa-Prieto, Isabel Ubeda-Bañon, and Susana Garcia-Muñozguren
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Olfactory system ,Male ,medicine.medical_specialty ,Pathology ,Parkinson's disease ,Cell Count ,Substance P ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Neurites ,Humans ,Aged ,Aged, 80 and over ,Cerebral Cortex ,biology ,Lewy body ,Olfactory tubercle ,Calcium-Binding Proteins ,Parkinson Disease ,Olfactory Pathways ,Middle Aged ,medicine.disease ,Olfactory Bulb ,Olfactory bulb ,Anterior olfactory nucleus ,Endocrinology ,nervous system ,Case-Control Studies ,biology.protein ,alpha-Synuclein ,Female ,Lewy Bodies ,Neurology (clinical) ,Olfactory ensheathing glia ,Parvalbumin - Abstract
Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.
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- 2009
50. Subicular and CA1 hippocampal projections to the accessory olfactory bulb
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Palma Pro-Sistiaga, C. de la Rosa-Prieto, Isabel Ubeda-Bañon, Alicia Mohedano-Moriano, Ricardo Insausti, Daniel Saiz-Sanchez, and Alino Martinez-Marcos
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Olfactory system ,Vomeronasal organ ,Cognitive Neuroscience ,Hippocampus ,Biotin ,Fluorescent Antibody Technique ,Hippocampal formation ,Biology ,Rats, Sprague-Dawley ,Neural Pathways ,Animals ,Neurons ,Rhodamines ,Olfactory tubercle ,Subiculum ,Dextrans ,Olfactory Pathways ,Entorhinal cortex ,Olfactory bulb ,Rats ,nervous system ,Female ,Vomeronasal Organ ,Somatostatin ,Neuroscience - Abstract
The hippocampal formation is anatomically and functionally related to the olfactory structures especially in rodents. The entorhinal cortex (EC) receives afferent projections from the main olfactory bulb; this constitutes an olfactory pathway to the hippocampus. In addition to the olfactory system, most mammals possess an accessory olfactory (or vomeronasal) system. The relationships between the hippocampal formation and the vomeronasal system are virtually unexplored. Recently, a centrifugal projection from CA1 to the accessory olfactory bulb has been identified using anterograde tracers. In the study reported herein, experiments using anterograde tracers confirm this projection, and injections of retrograde tracers show the distribution and morphology of a population of CA1 and ventral subicular neurons projecting to the accessory olfactory bulb of rats. These results extend previous descriptions of hippocampal projections to the accessory olfactory bulb by including the ventral subiculum and characterizing the morphology, neurochemistry (double labeling with somatostatin), and distribution of such neurons. These data suggest feedback hippocampal control of chemosensory stimuli in the accessory olfactory bulb. Whether this projection processes spatial information on conspecifics or is involved in learning and memory processes associated with chemical stimuli remains to be elucidated. © 2008 Wiley-Liss, Inc.
- Published
- 2008
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