16 results on '"Isabel Ubeda-Banon"'
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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. 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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6. 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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7. 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.
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- 2021
8. Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation
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Emilio Llanos-González, Francisco J. Sancho-Bielsa, Javier Frontiñán-Rubio, Yoana Rabanal-Ruíz, Sonia García-Carpintero, Eduardo Chicano, Isabel Úbeda-Banon, Alicia Flores-Cuadrado, Lydia Giménez-Llort, Francisco Javier Alcaín, Juan Ramón Peinado, and Mario Durán-Prado
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3xTg-AD mice ,Alzheimer’s disease ,coenzyme Q10 ,MALDI-imaging ,mass spectrometry ,ubiquinol ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI–MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.
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- 2023
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9. 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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10. 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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11. Anxiety levels among health sciences students during their first visit to the dissection room
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Carmen Romo-Barrientos, Juan José Criado-Álvarez, Jaime González-González, Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Daniel Saiz-Sánchez, Antonio Viñuela, Jose Luis Martin-Conty, Teresa Simón, Alino Martinez-Marcos, and Alicia Mohedano-Moriano
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Anatomy education ,Dissection ,Prosection ,Anxiety ,Health sciences ,Special aspects of education ,LC8-6691 ,Medicine - Abstract
Abstract Background The teaching of human anatomy is often based on practices of cadaver dissection and prosected specimens. However, exposure to human cadavers might be stressful and anxiety-inducing for students. The aim of this study is to explore the degree of satisfaction and anxiety among first-year students in the Medicine, Occupational Therapy, Speech Therapy and Nursing programmes at the Universidad de Castilla-La Mancha (Spain) who are experiencing their first dissection/prosection practice to develop stress coping strategies. Methods A total of 204 health sciences students participated in this study. The State-Trait Anxiety Inventory was used to evaluate anxiety. Results ‘State Anxiety’ (SA) decreased significantly throughout the course (p
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- 2020
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12. The Effect of Visualization Techniques on Students of Occupational Therapy during the First Visit to the Dissection Room
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Juan José Criado-Álvarez, Carmen Romo-Barrientos, Carmen Zabala-Baños, Manuela Martínez-Lorca, Antonio Viñuela, Isabel Ubeda-Bañon, Alicia Flores-Cuadrado, Alberto Martínez-Lorca, Begoña Polonio-López, and Alicia Mohedano-Moriano
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anatomy ,visualization technique ,prosection ,cadaver ,anxiety ,occupation ,Medicine - Abstract
Background: Part of the basic teaching of human anatomy are prosection sessions with a human corpse, which may generate stress or anxiety among students. The objective of this work was to study how, through the visualization technique (a coping technique), these levels could be reduced before starting prosection classes. Methods: A cross-sectional pilot study was conducted involving first-year students who had never participated in screening sessions. Prior to the visit, occupational therapy students underwent a viewing session (visualization technique). On the day of the visit, before and after the screening session, an anonymous questionnaire was distributed to find out about aspects of the students’ experiences, such as their feelings and perceptions. The State–Trait Anxiety Inventory was used to assess anxiety. Results: The baseline levels of anxiety measured remained stable (from 18.5 to 18.2 points), with no differences being found (p > 0.05). The levels of emotional anxiety measured fell from 15.2 to 12.6 points (p < 0.05). Before starting the class, there were six students (17.1%) with anxiety criteria, and this figure was doubled at the end of the session (33.3%) (p < 0.05). Conclusions: Sessions in a dissection room can cause stressful experiences and change the emotional balances of some students. The results obtained and published here showed no significant differences after the visualization technique. We found that the students believed that the prosection sessions were very useful for teaching anatomy.
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- 2022
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13. Human amyloid-β enriched extracts: evaluation of in vitro and in vivo internalization and molecular characterization
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Cristina M. Pedrero-Prieto, Alicia Flores-Cuadrado, Daniel Saiz-Sánchez, Isabel Úbeda-Bañón, Javier Frontiñán-Rubio, Francisco J. Alcaín, Lourdes Mateos-Hernández, José de la Fuente, Mario Durán-Prado, Margarita Villar, Alino Martínez-Marcos, and Juan R. Peinado
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Alzheimer’s disease ,Amyloid-β ,Prion-like hypothesis ,Amyloid-β internalization ,Proteomics ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
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
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- 2019
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14. 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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15. 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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16. 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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