158 results on '"Humans"'
Search Results
2. Special Issue "Aquaporins in Brain Disease".
- Author
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Echevarría M and García-Miranda P
- Subjects
- Humans, Water metabolism, Homeostasis, Brain metabolism, Aquaporins metabolism, Brain Diseases
- Abstract
Water is an abundant and important component of the human brain, the homeostasis of which is rigorously controlled [...].
- Published
- 2024
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3. Flapping Tremor: Unraveling Asterixis-A Narrative Review.
- Author
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Rissardo JP, Muhammad S, Yatakarla V, Vora NM, Paras P, and Caprara ALF
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- Humans, Tremor diagnosis, Tremor etiology, Carbamazepine therapeutic use, Myoclonus diagnosis, Dyskinesias, Brain Diseases
- Abstract
Asterixis is a subtype of negative myoclonus characterized by brief, arrhythmic lapses of sustained posture due to involuntary pauses in muscle contraction. We performed a narrative review to characterize further asterixis regarding nomenclature, historical aspects, etiology, pathophysiology, classification, diagnosis, and treatment. Asterixis has been classically used as a synonym for negative myoclonus across the literature and in previous articles. However, it is important to distinguish asterixis from other subtypes of negative myoclonus, for example, epileptic negative myoclonus, because management could change. Asterixis is not specific to any pathophysiological process, but it is more commonly reported in hepatic encephalopathy, renal and respiratory failure, cerebrovascular diseases, as well as associated with drugs that could potentially lead to hyperammonemia, such as valproic acid, carbamazepine, and phenytoin. Asterixis is usually asymptomatic and not spontaneously reported by patients. This highlights the importance of actively searching for this sign in the physical exam of encephalopathic patients because it could indicate an underlying toxic or metabolic cause. Asterixis is usually reversible upon treatment of the underlying cause.
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- 2024
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4. Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies.
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Lamanna J and Meldolesi J
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- Humans, Child, Preschool, Child, Brain, Neurons, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder genetics, Autism Spectrum Disorder therapy, Autistic Disorder, Brain Diseases
- Abstract
Autism spectrum disorder (ASD), affecting over 2% of the pre-school children population, includes an important fraction of the conditions accounting for the heterogeneity of autism. The disease was discovered 75 years ago, and the present review, based on critical evaluations of the recognized ASD studies from the beginning of 1990, has been further developed by the comparative analyses of the research and clinical reports, which have grown progressively in recent years up to late 2023. The tools necessary for the identification of the ASD disease and its related clinical pathologies are genetic and epigenetic mutations affected by the specific interaction with transcription factors and chromatin remodeling processes occurring within specific complexes of brain neurons. Most often, the ensuing effects induce the inhibition/excitation of synaptic structures sustained primarily, at dendritic fibers, by alterations of flat and spine response sites. These effects are relevant because synapses, established by specific interactions of neurons with glial cells, operate as early and key targets of ASD. The pathology of children is often suspected by parents and communities and then confirmed by ensuing experiences. The final diagnoses of children and mature patients are then completed by the combination of neuropsychological (cognitive) tests and electro-/magneto-encephalography studies developed in specialized centers. ASD comorbidities, induced by processes such as anxieties, depressions, hyperactivities, and sleep defects, interact with and reinforce other brain diseases, especially schizophrenia. Advanced therapies, prescribed to children and adult patients for the control of ASD symptoms and disease, are based on the combination of well-known brain drugs with classical tools of neurologic and psychiatric practice. Overall, this review reports and discusses the advanced knowledge about the biological and medical properties of ASD.
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- 2024
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5. Resveratrol Alleviates the Early Challenges of Implant-Based Drug Delivery in a Human Glial Cell Model.
- Author
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Schlotterose L, Cossais F, Lucius R, and Hattermann K
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- Humans, Resveratrol pharmacology, Resveratrol metabolism, Astrocytes metabolism, Microglia metabolism, Oxygen metabolism, Neuroglia metabolism, Brain Diseases metabolism
- Abstract
Brain diseases are oftentimes life-threatening and difficult to treat. The local administration of drug substances using brain implants can increase on-site concentrations and decrease systemic side effects. However, the biocompatibility of potential brain implant materials needs to be evaluated carefully as implants can trigger foreign body reactions, particularly by increasing the microglia and astrocyte reactivity. To date, these tests have been frequently conducted in very simple in vitro models, in particular not respecting the key players in glial cell reactions and the challenges of surgical implantation characterized by the disruption of oxygen and nutrient supply. Thus, we established an in vitro model in which we treated human glial cell lines with reduced oxygen and glucose levels. The model displayed cytokine and reactive oxygen species release from reactive microglia and an increase in a marker of reactive astrocytes, galectin-3. Moreover, the treatment caused changes in the cell survival and triggered the production of hypoxia-inducible factor 1α. In this comprehensive platform, we demonstrated the protective effect of the natural polyphenol resveratrol as a model substance, which might be included in brain implants to ease the undesired glial cell response. Overall, a glial-cell-based in vitro model of the initial challenges of local brain disease treatment may prove useful for investigating new therapy options.
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- 2024
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6. Atypical Complications during the Course of COVID-19: A Comprehensive Review.
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Mallhi TH, Safdar A, Butt MH, Salman M, Nosheen S, Mustafa ZU, Khan FU, and Khan YH
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- Humans, Ischemia, COVID-19 complications, Ischemic Stroke, Acute Kidney Injury epidemiology, Acute Kidney Injury etiology, Brain Diseases
- Abstract
COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49-83.87%), GI bleeding/hemorrhage (IR: 0.47-10.6%), hepatic ischemia (IR: 1.0-7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5-90.9%), anosmia (IR: 4.9-79.6%), dysgeusia (IR: 2.8-83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19-35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5-68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2-55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9-16.7%), and coagulopathy/venous thromboembolism (IR: 19-34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.
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- 2024
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7. Dual-Planar Monopole Antenna-Based Remote Sensing System for Microwave Medical Applications.
- Author
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Zhao M, Riaz A, Saied IM, Shami Z, and Arslan T
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- Humans, Remote Sensing Technology, Algorithms, Brain, Microwaves, Brain Diseases
- Abstract
Neurodegenerative diseases (NDs) can be life threatening and have chronic impacts on patients and society. Timely diagnosis and treatment are imperative to prevent deterioration. Conventional imaging modalities, such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron Emission Tomography (PET), are expensive and not readily accessible to patients. Microwave sensing and imaging (MSI) systems are promising tools for monitoring pathological changes, namely the lateral ventricle enlargement associated with ND, in a non-invasive and convenient way. This paper presents a dual-planar monopole antenna-based remote sensing system for ND monitoring. First, planar monopole antennas were designed using the simulation software CST Studio Suite. The antenna analysis was carried out regarding the reflection coefficient, gain, radiation pattern, time domain characterization, E-field distribution, and Specific Absorption Rate (SAR). The designed antennas were then integrated with a controlling circuit as a remote sensing system. The system was experimentally validated on brain phantoms using a vector network analyzer and a laptop. The collected reflection coefficient data were processed using a radar-based imaging algorithm to reconstruct images indicating brain abnormality in ND. The results suggest that the system could serve as a low-cost and efficient tool for long-term monitoring of ND, particularly in clinics and care home scenarios.
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- 2024
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8. Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases.
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Jayanti S, Vitek L, Verde CD, Llido JP, Sukowati C, Tiribelli C, and Gazzin S
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- Adult, Aged, Humans, Liver, Bilirubin, Biliverdine, Heme, Heme Oxygenase (Decyclizing), Health Promotion, Brain Diseases
- Abstract
The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.
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- 2024
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9. Epileptic Encephalopathy GABRB Structural Variants Share Common Gating and Trafficking Defects.
- Author
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Hernandez CC, Hu N, Shen W, and Macdonald RL
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- Humans, Mutation, Missense, Mutation, Seizures, Receptors, GABA-A metabolism, Brain Diseases
- Abstract
Variants in the GABRB gene, which encodes the β subunit of the GABA
A receptor, have been implicated in various epileptic encephalopathies and related neurodevelopmental disorders such as Dravet syndrome and Angelman syndrome. These conditions are often associated with early-onset seizures, developmental regression, and cognitive impairments. The severity and specific features of these encephalopathies can differ based on the nature of the genetic variant and its impact on GABAA receptor function. These variants can lead to dysfunction in GABAA receptor-mediated inhibition, resulting in an imbalance between neuronal excitation and inhibition that contributes to the development of seizures. Here, 13 de novo EE-associated GABRB variants, occurring as missense mutations, were analyzed to determine their impact on protein stability and flexibility, channel function, and receptor biogenesis. Our results showed that all mutations studied significantly impact the protein structure, altering protein stability, flexibility, and function to varying degrees. Variants mapped to the GABA-binding domain, coupling zone, and pore domain significantly impact the protein structure, modifying the β+/α- interface of the receptor and altering channel activation and receptor trafficking. Our study proposes that the extent of loss or gain of GABAA receptor function can be elucidated by identifying the specific structural domain impacted by mutation and assessing the variability in receptor structural dynamics. This paves the way for future studies to explore and uncover links between the incidence of a variant in the receptor topology and the severity of the related disease.- Published
- 2023
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10. Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder.
- Author
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Tizabi Y, Bennani S, El Kouhen N, Getachew B, and Aschner M
- Subjects
- Adolescent, Humans, Child, Preschool, Lead toxicity, Brain, Gastrointestinal Microbiome, Autism Spectrum Disorder etiology, Brain Diseases
- Abstract
Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and communication, manifests in early childhood and is followed by restricted and stereotyped behaviors, interests, or activities in adolescence and adulthood (DSM-V). Although genetics and environmental factors have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes, including anemia, encephalopathy, gastroenteric diseases, and, more importantly, cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as the "Gut-Brain Axis (GBA)". In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. The potential exploitation of this interaction for therapeutic purposes is also touched upon.
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- 2023
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11. Polyomavirus Wakes Up and Chooses Neurovirulence.
- Author
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Butic AB, Spencer SA, Shaheen SK, and Lukacher AE
- Subjects
- Humans, Animals, Mice, Polyomavirus, Leukoencephalopathy, Progressive Multifocal, JC Virus, Polyomavirus Infections, Brain Diseases
- Abstract
JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has "reemerged" as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.
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- 2023
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12. Clinical Cases and the Molecular Profiling of a Novel Childhood Encephalopathy-Causing GNAO1 Mutation P170R.
- Author
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Larasati YA, Solis GP, Koval A, Griffiths ST, Berentsen R, Aukrust I, Lesca G, Chatron N, Ville D, Korff CM, and Katanaev VL
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- Humans, Child, Mutation genetics, GTP-Binding Proteins metabolism, Ions metabolism, Guanosine Triphosphate, GTP-Binding Protein alpha Subunits, Gi-Go genetics, GTP-Binding Protein alpha Subunits, Gi-Go metabolism, Brain Diseases
- Abstract
De novo mutations in GNAO1 , the gene encoding the major neuronal G protein Gαo, cause a spectrum of pediatric encephalopathies with seizures, motor dysfunction, and developmental delay. Of the >80 distinct missense pathogenic variants, many appear to uniformly destabilize the guanine nucleotide handling of the mutant protein, speeding up GTP uptake and deactivating GTP hydrolysis. Zinc supplementation emerges as a promising treatment option for this disease, as Zn
2+ ions reactivate the GTP hydrolysis on the mutant Gαo and restore cellular interactions for some of the mutants studied earlier. The molecular etiology of GNAO1 encephalopathies needs further elucidation as a prerequisite for the development of efficient therapeutic approaches. In this work, we combine clinical and medical genetics analysis of a novel GNAO1 mutation with an in-depth molecular dissection of the resultant protein variant. We identify two unrelated patients from Norway and France with a previously unknown mutation in GNAO1 , c.509C>G that results in the production of the Pro170Arg mutant Gαo, leading to severe developmental and epileptic encephalopathy. Molecular investigations of Pro170Arg identify this mutant as a unique representative of the pathogenic variants. Its 100-fold-accelerated GTP uptake is not accompanied by a loss in GTP hydrolysis; Zn2+ ions induce a previously unseen effect on the mutant, forcing it to lose the bound GTP. Our work combining clinical and molecular analyses discovers a novel, biochemically distinct pathogenic missense variant of GNAO1 laying the ground for personalized treatment development.- Published
- 2023
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13. Sex Differences in Brain Disorders.
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Ziemka-Nalecz M, Pawelec P, Ziabska K, and Zalewska T
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- Humans, Male, Female, Brain, Sex Characteristics, Brain Diseases
- Abstract
A remarkable feature of the brain is its sexual dimorphism. Sexual dimorphism in brain structure and function is associated with clinical implications documented previously in healthy individuals but also in those who suffer from various brain disorders. Sex-based differences concerning some features such as the risk, prevalence, age of onset, and symptomatology have been confirmed in a range of neurological and neuropsychiatric diseases. The mechanisms responsible for the establishment of sex-based differences between men and women are not fully understood. The present paper provides up-to-date data on sex-related dissimilarities observed in brain disorders and highlights the most relevant features that differ between males and females. The topic is very important as the recognition of disparities between the sexes might allow for the identification of therapeutic targets and pharmacological approaches for intractable neurological and neuropsychiatric disorders.
- Published
- 2023
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14. Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders.
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Arjmand S, Bender D, Jakobsen S, Wegener G, and Landau AM
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- Humans, Estradiol, Positron-Emission Tomography, Brain diagnostic imaging, Brain metabolism, Receptors, Estrogen metabolism, Brain Diseases
- Abstract
Estrogen receptors (ERs) play a multitude of roles in brain function and are implicated in various brain disorders. The use of positron emission tomography (PET) tracers for the visualization of ERs' intricate landscape has shown promise in oncology but remains limited in the context of brain disorders. Despite recent progress in the identification and development of more selective ligands for various ERs subtypes, further optimization is necessary to enable the reliable and efficient imaging of these receptors. In this perspective, we briefly touch upon the significance of estrogen signaling in the brain and raise the setbacks associated with the development of PET tracers for identification of specific ERs subtypes in the brain. We then propose avenues for developing efficient PET tracers to non-invasively study the dynamics of ERs in the brain, as well as neuropsychiatric diseases associated with their malfunction in a longitudinal manner. This perspective puts several potential candidates on the table and highlights the unmet needs and areas requiring further research to unlock the full potential of PET tracers for ERs imaging, ultimately aiding in deepening our understanding of ERs and forging new avenues for potential therapeutic strategies.
- Published
- 2023
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15. Advanced Techniques Using In Vivo Electroporation to Study the Molecular Mechanisms of Cerebral Development Disorders.
- Author
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Yang C, Shitamukai A, Yang S, and Kawaguchi A
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- Animals, Female, Humans, Gene Editing methods, Electroporation Therapies, Cerebral Cortex physiology, Mammals, Electroporation methods, Brain Diseases genetics
- Abstract
The mammalian cerebral cortex undergoes a strictly regulated developmental process. Detailed in situ visualizations, imaging of these dynamic processes, and in vivo functional gene studies significantly enhance our understanding of brain development and related disorders. This review introduces basic techniques and recent advancements in in vivo electroporation for investigating the molecular mechanisms underlying cerebral diseases. In utero electroporation (IUE) is extensively used to visualize and modify these processes, including the forced expression of pathological mutants in human diseases; thus, this method can be used to establish animal disease models. The advent of advanced techniques, such as genome editing, including de novo knockout, knock-in, epigenetic editing, and spatiotemporal gene regulation, has further expanded our list of investigative tools. These tools include the iON expression switch for the precise control of timing and copy numbers of exogenous genes and TEMPO for investigating the temporal effects of genes. We also introduce the iGONAD method, an improved genome editing via oviductal nucleic acid delivery approach, as a novel genome-editing technique that has accelerated brain development exploration. These advanced in vivo electroporation methods are expected to provide valuable insights into pathological conditions associated with human brain disorders.
- Published
- 2023
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16. 3' UTR Deletion of FBXO28 in a Patient with Brain Abnormalities and Developmental Delay.
- Author
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Bi X, Mulhern MS, Spiegel E, Wapner RJ, Levy B, Bain JM, and Liao J
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- Female, Pregnancy, Humans, 3' Untranslated Regions genetics, Seizures, Oligonucleotides, Brain, SKP Cullin F-Box Protein Ligases, Brain Diseases, Intellectual Disability genetics, Nervous System Malformations
- Abstract
Constitutional deletions of chromosome 1q42 region are rare. The phenotype spectrum associated with this copy number change is variable, including developmental delay, intellectual disability, seizures, and dysmorphology. This study describes a patient with developmental delays and brain abnormalities. G-banded karyotype, FISH, SNP oligonucleotide microarray analysis (SOMA), and whole exome sequencing analysis were performed. Postnatal reanalysis of prenatal SOMA and follow-up parental testing revealed a paternally inherited 63 kb deletion at 1q42.11 in the patient. We characterized the clinical features of this patient, providing insight into the clinical phenotype associated with deletions of the 1q42.11 sub-band. Our study provides new evidence supporting the potential functional importance of the FBXO28 3' UTR region and the hypothesis that FBXO28 is a critical gene in the pathogenesis of chromosome 1q41q42 microdeletion syndrome. It also highlights the different goals and reporting criteria between prenatal and postnatal microarray tests.
- Published
- 2023
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17. Microglia and Brain Disorders: The Role of Vitamin D and Its Receptor.
- Author
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Mirarchi A, Albi E, Beccari T, and Arcuri C
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- Humans, Microglia metabolism, Vitamin D metabolism, Central Nervous System metabolism, Brain metabolism, Vitamins metabolism, Autism Spectrum Disorder metabolism, Brain Diseases metabolism
- Abstract
Accounting for 5-20% of the total glial cells present in the adult brain, microglia are involved in several functions: maintenance of the neural environment, response to injury and repair, immunesurveillance, cytokine secretion, regulation of phagocytosis, synaptic pruning, and sculpting postnatal neural circuits. Microglia contribute to some neurodevelopmental disorders, such as Nasu-Hakola disease (NHD), Tourette syndrome (TS), autism spectrum disorder (ASD), and schizophrenia. Moreover, microglial involvement in neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, has also been well established. During the last two decades, epidemiological and research studies have demonstrated the involvement of vitamin D3 (VD3) in the brain's pathophysiology. VD3 is a fat-soluble metabolite that is required for the proper regulation of many of the body's systems, as well as for normal human growth and development, and shows neurotrophic and neuroprotective actions and influences on neurotransmission and synaptic plasticity, playing a role in various neurological diseases. In order to better understand the exact mechanisms behind the diverse actions of VD3 in the brain, a large number of studies have been performed on isolated cells or tissues of the central nervous system (CNS). Here, we discuss the involvement of VD3 and microglia on neurodegeneration- and aging-related diseases.
- Published
- 2023
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18. Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.
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Farcy S, Hachour H, Bahi-Buisson N, and Passemard S
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- Humans, Centrosome metabolism, Brain metabolism, Body Size, Nerve Tissue Proteins metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Microcephaly genetics, Microcephaly metabolism, Brain Diseases metabolism
- Abstract
Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins.
- Published
- 2023
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19. The Genetics of Primary Familial Brain Calcification: A Literature Review.
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Chen SY, Ho CJ, Lu YT, Lin CH, Lan MY, and Tsai MH
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- Humans, Brain diagnostic imaging, Brain pathology, Phenotype, Proto-Oncogene Proteins c-sis genetics, Mutation, Sodium-Phosphate Cotransporter Proteins, Type III genetics, Brain Diseases genetics, Brain Diseases pathology, Basal Ganglia Diseases pathology
- Abstract
Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes ( SLC20A2 , PDGFRB , PDGFB , and XPR1 ) and three recessive inherited genes ( MYORG , JAM2 , and CMPK2 ). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies.
- Published
- 2023
- Full Text
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20. Deletion of a Single Lysine Residue at Position 292 of CAMK2A Disrupts Protein Function, Causing Severe Epileptic Encephalopathy and Intellectual Disability.
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Lintas C, Facchiano A, Azzarà A, Cassano I, Tabolacci C, Galasso C, and Gurrieri F
- Subjects
- Female, Humans, Lysine, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Intellectual Disability genetics, Intellectual Disability pathology, Neurodevelopmental Disorders genetics, Brain Diseases
- Abstract
Background: The use of NGS technology has rapidly increased during the last decade, and many new monogenic neurodevelopmental disorders have emerged. Pathogenic variants in the neuronal CAMK2A gene have been recently associated with "intellectual developmental disorder, autosomal dominant 53″ (OMIM#617798), a syndrome characterized by variable clinical manifestations including mild to severe intellectual disability, delayed psychomotor development, delayed or absent speech, delayed walking, seizures, dysmorphic features and behavioral psychiatric manifestations as autism spectrum disorders, aggressive behavior, and hyperactivity. CAMK2A (OMIM*114078) encodes for a subunit of the calcium/calmodulin-dependent serine/threonine kinase II (CaMKII), which is predominately expressed in the brain, where it plays critical roles in synaptic plasticity, learning, and memory as well as in neuronal migration., Methods and Results: We hereby describe a thirty-five-year-old woman affected by severe intellectual disability with epileptic encephalopathy. We performed exome sequencing and found a de novo heterozygous variant in the CAMK2A gene (NM_171825.2: c.874_876delCTT; p.Lys292del), which was fully correlated with her phenotype. This is the first report of an inframe single amino acid deletion in a patient affected by intellectual developmental disorder autosomal dominant 53. The variant is predicted to affect protein structure and function and interaction with other proteins and hits a crucial functional site., Discussion: We discuss our variant in relation to previously reported variants and with the objective of delineating possible genotype-phenotype correlations.
- Published
- 2023
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21. The Emerging Roles of the Cephalic Neural Crest in Brain Development and Developmental Encephalopathies.
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Bruet E, Amarante-Silva D, Gorojankina T, and Creuzet S
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- Animals, Humans, Prosencephalon, Vertebrates, Gene Expression Regulation, Developmental, Neural Crest, Brain Diseases
- Abstract
The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on the development of the forebrain and sense organs. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.
- Published
- 2023
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22. Imaging Approaches to Investigate Pathophysiological Mechanisms of Brain Disease in Zebrafish.
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Turrini L, Roschi L, de Vito G, Pavone FS, and Vanzi F
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- Animals, Humans, Zebrafish genetics, Disease Models, Animal, Brain diagnostic imaging, Brain physiology, Brain Diseases diagnostic imaging, Nervous System Diseases diagnostic imaging
- Abstract
Zebrafish has become an essential model organism in modern biomedical research. Owing to its distinctive features and high grade of genomic homology with humans, it is increasingly employed to model diverse neurological disorders, both through genetic and pharmacological intervention. The use of this vertebrate model has recently enhanced research efforts, both in the optical technology and in the bioengineering fields, aiming at developing novel tools for high spatiotemporal resolution imaging. Indeed, the ever-increasing use of imaging methods, often combined with fluorescent reporters or tags, enable a unique chance for translational neuroscience research at different levels, ranging from behavior (whole-organism) to functional aspects (whole-brain) and down to structural features (cellular and subcellular). In this work, we present a review of the imaging approaches employed to investigate pathophysiological mechanisms underlying functional, structural, and behavioral alterations of human neurological diseases modeled in zebrafish.
- Published
- 2023
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23. Brain Calcifications: Genetic, Molecular, and Clinical Aspects.
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Monfrini E, Arienti F, Rinchetti P, Lotti F, and Riboldi GM
- Subjects
- Humans, Xenotropic and Polytropic Retrovirus Receptor, Calcium metabolism, Brain metabolism, Molecular Biology, Mutation, Sodium-Phosphate Cotransporter Proteins, Type III genetics, Brain Diseases metabolism, Calcinosis genetics, Calcinosis metabolism
- Abstract
Many conditions can present with accumulation of calcium in the brain and manifest with a variety of neurological symptoms. Brain calcifications can be primary (idiopathic or genetic) or secondary to various pathological conditions (e.g., calcium-phosphate metabolism derangement, autoimmune disorders and infections, among others). A set of causative genes associated with primary familial brain calcification (PFBC) has now been identified, and include genes such as SLC20A2 , PDGFB , PDGFRB , XPR1 , MYORG , and JAM2 . However, many more genes are known to be linked with complex syndromes characterized by brain calcifications and additional neurologic and systemic manifestations. Of note, many of these genes encode for proteins involved in cerebrovascular and blood-brain barrier functions, which both represent key anatomical structures related to these pathological phenomena. As a growing number of genes associated with brain calcifications is identified, pathways involved in these conditions are beginning to be understood. Our comprehensive review of the genetic, molecular, and clinical aspects of brain calcifications offers a framework for clinicians and researchers in the field.
- Published
- 2023
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24. Multidomain Convolution Neural Network Models for Improved Event-Related Potential Classification.
- Author
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Chen X, Gupta RS, and Gupta L
- Subjects
- Humans, Brain, Evoked Potentials, Neural Networks, Computer, Artifacts, Brain Diseases
- Abstract
Two convolution neural network (CNN) models are introduced to accurately classify event-related potentials (ERPs) by fusing frequency, time, and spatial domain information acquired from the continuous wavelet transform (CWT) of the ERPs recorded from multiple spatially distributed channels. The multidomain models fuse the multichannel Z-scalograms and the V-scalograms, which are generated from the standard CWT scalogram by zeroing-out and by discarding the inaccurate artifact coefficients that are outside the cone of influence (COI), respectively. In the first multidomain model, the input to the CNN is generated by fusing the Z-scalograms of the multichannel ERPs into a frequency-time-spatial cuboid. The input to the CNN in the second multidomain model is formed by fusing the frequency-time vectors of the V-scalograms of the multichannel ERPs into a frequency-time-spatial matrix. Experiments are designed to demonstrate (a) customized classification of ERPs, where the multidomain models are trained and tested with the ERPs of individual subjects for brain-computer interface (BCI)-type applications, and (b) group-based ERP classification, where the models are trained on the ERPs from a group of subjects and tested on single subjects not included in the training set for applications such as brain disorder classification. Results show that both multidomain models yield high classification accuracies for single trials and small-average ERPs with a small subset of top-ranked channels, and the multidomain fusion models consistently outperform the best unichannel classifiers.
- Published
- 2023
- Full Text
- View/download PDF
25. The Microbiota-Gut-Brain Axis in Behaviour and Brain Disorders.
- Author
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Lana D and Giovannini MG
- Subjects
- Humans, Brain microbiology, Brain-Gut Axis, Gastrointestinal Microbiome, Brain Diseases, Microbiota
- Abstract
The gut, along with its microbiota (MB-gut), is the largest absorption organ and reservoir of bacteria in the human body [...].
- Published
- 2023
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26. Extracellular Matrix Regulation in Physiology and in Brain Disease.
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Soles A, Selimovic A, Sbrocco K, Ghannoum F, Hamel K, Moncada EL, Gilliat S, and Cvetanovic M
- Subjects
- Humans, Brain metabolism, Extracellular Matrix metabolism, Brain Diseases genetics, Brain Diseases metabolism
- Abstract
The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on "omic" approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling.
- Published
- 2023
- Full Text
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27. An Update of Epigenetic Drugs for the Treatment of Cancers and Brain Diseases: A Comprehensive Review.
- Author
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Sahafnejad Z, Ramazi S, and Allahverdi A
- Subjects
- Humans, Histones genetics, Histones metabolism, DNA Methylation, Epigenesis, Genetic, Neoplasms drug therapy, Neoplasms genetics, Brain Diseases genetics
- Abstract
Epigenetics has long been recognized as a significant field in biology and is defined as the investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA methylation, play crucial roles in gene regulation. Numerous studies in humans have been carried out on single-nucleotide resolution of DNA methylation, the CpG island, new histone modifications, and genome-wide nucleosome positioning. These studies indicate that epigenetic mutations and aberrant placement of these epigenetic marks play a critical role in causing the disease. Consequently, significant development has occurred in biomedical research in identifying epigenetic mechanisms, their interactions, and changes in health and disease conditions. The purpose of this review article is to provide comprehensive information about the different types of diseases caused by alterations in epigenetic factors such as DNA methylation and histone acetylation or methylation. Recent studies reported that epigenetics could influence the evolution of human cancer via aberrant methylation of gene promoter regions, which is associated with reduced gene function. Furthermore, DNA methyltransferases (DNMTs) in the DNA methylation process as well as histone acetyltransferases (HATs)/histone deacetylases (HDACs) and histone methyltransferases (HMTs)/demethylases (HDMs) in histone modifications play important roles both in the catalysis and inhibition of target gene transcription and in many other DNA processes such as repair, replication, and recombination. Dysfunction in these enzymes leads to epigenetic disorders and, as a result, various diseases such as cancers and brain diseases. Consequently, the knowledge of how to modify aberrant DNA methylation as well as aberrant histone acetylation or methylation via inhibitors by using epigenetic drugs can be a suitable therapeutic approach for a number of diseases. Using the synergistic effects of DNA methylation and histone modification inhibitors, it is hoped that many epigenetic defects will be treated in the future. Numerous studies have demonstrated a link between epigenetic marks and their effects on brain and cancer diseases. Designing appropriate drugs could provide novel strategies for the management of these diseases in the near future.
- Published
- 2023
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28. High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy.
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DeWulf B, Minsart L, Verdonk F, Kruys V, Piagnerelli M, Maze M, and Saxena S
- Subjects
- Humans, Alarmins, Sepsis-Associated Encephalopathy diagnosis, HMGB1 Protein, Sepsis complications, Sepsis pathology, Brain Diseases
- Abstract
Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood-brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.
- Published
- 2023
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29. Phenotypes and Genotypes in Patients with SMC1A -Related Developmental and Epileptic Encephalopathy.
- Author
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Bozarth XL, Lopez J, Fang H, Lee-Eng J, Duan Z, and Deng X
- Subjects
- Male, Female, Humans, Genes, cdc, Genotype, Phenotype, De Lange Syndrome genetics, Brain Diseases genetics
- Abstract
The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A -DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A -DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A -DEE variants is closely associated with the manifestation of DEE phenotypes.
- Published
- 2023
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- View/download PDF
30. Glia-Neurotrophic Factor Relationships: Possible Role in Pathobiology of Neuroinflammation-Related Brain Disorders.
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Palasz E, Wilkaniec A, Stanaszek L, Andrzejewska A, and Adamczyk A
- Subjects
- Humans, Neuroinflammatory Diseases, Nerve Growth Factors metabolism, Neuroglia metabolism, Neurons metabolism, Transforming Growth Factor beta metabolism, Brain Diseases metabolism, Central Nervous System Diseases etiology, Central Nervous System Diseases metabolism
- Abstract
Neurotrophic factors (NTFs) play an important role in maintaining homeostasis of the central nervous system (CNS) by regulating the survival, differentiation, maturation, and development of neurons and by participating in the regeneration of damaged tissues. Disturbances in the level and functioning of NTFs can lead to many diseases of the nervous system, including degenerative diseases, mental diseases, and neurodevelopmental disorders. Each CNS disease is characterized by a unique pathomechanism, however, the involvement of certain processes in its etiology is common, such as neuroinflammation, dysregulation of NTFs levels, or mitochondrial dysfunction. It has been shown that NTFs can control the activation of glial cells by directing them toward a neuroprotective and anti-inflammatory phenotype and activating signaling pathways responsible for neuronal survival. In this review, our goal is to outline the current state of knowledge about the processes affected by NTFs, the crosstalk between NTFs, mitochondria, and the nervous and immune systems, leading to the inhibition of neuroinflammation and oxidative stress, and thus the inhibition of the development and progression of CNS disorders.
- Published
- 2023
- Full Text
- View/download PDF
31. The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms.
- Author
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Chiang MC, Tsai TY, and Wang CJ
- Subjects
- Neuroinflammatory Diseases chemically induced, Neuroinflammatory Diseases prevention & control, Neurodegenerative Diseases chemically induced, Neurodegenerative Diseases prevention & control, Particulate Matter toxicity, Animals, Mice, Rats, Humans, Quercetin pharmacology, Quercetin therapeutic use, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Brain Diseases chemically induced, Brain Diseases prevention & control, Neuroprotection
- Abstract
Neuroinflammation is a critical factor in developing and progressing numerous brain diseases, including neurodegenerative diseases. Chronic or excessive neuroinflammation can lead to neurotoxicity, causing brain damage and contributing to the onset and progression of various brain diseases. Therefore, understanding neuroinflammation mechanisms and developing strategies to control them is crucial for treating brain diseases. Studies have shown that neuroinflammation plays a vital role in the progression of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD), and stroke. Additionally, the effects of PM
2.5 pollution on the brain, including neuroinflammation and neurotoxicity, are well-documented. Quercetin is a flavonoid, a plant pigment in many fruits, vegetables, and grains. Quercetin has been studied for its potential health benefits, including its anti-inflammatory, antioxidant, and anti-cancer properties. Quercetin may also have a positive impact on immune function and allergy symptoms. In addition, quercetin has been shown to have anti-inflammatory and neuroprotective properties and can activate AMP-activated protein kinase (AMPK), a cellular energy sensor that modulates inflammation and oxidative stress. By reducing inflammation and protecting against neuroinflammatory toxicity, quercetin holds promise as a safe and effective adjunctive therapy for treating neurodegenerative diseases and other brain disorders. Understanding and controlling the mechanisms of NF-κB and NLRP3 inflammasome pathways are crucial for preventing and treating conditions, and quercetin may be a promising tool in this effort. This review article aims to discuss the role of neuroinflammation in the development and progression of various brain disorders, including neurodegenerative diseases and stroke, and the impact of PM2.5 pollution on the brain. The paper also highlights quercetin's potential health benefits and anti-inflammatory and neuroprotective properties.- Published
- 2023
- Full Text
- View/download PDF
32. Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature.
- Author
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Phing AH, Makpol S, Nasaruddin ML, Wan Zaidi WA, Ahmad NS, and Embong H
- Subjects
- Humans, Aged, Tryptophan metabolism, Kynurenine metabolism, Immune System metabolism, Quinolinic Acid metabolism, Brain Diseases, Delirium etiology
- Abstract
Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.
- Published
- 2023
- Full Text
- View/download PDF
33. Independent Associated SNPs at SORCS3 and Its Protein Interactors for Multiple Brain-Related Disorders and Traits.
- Author
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Kamran M, Laighneach A, Bibi F, Donohoe G, Ahmed N, Rehman AU, and Morris DW
- Subjects
- Humans, Brain metabolism, Phenotype, Polymorphism, Single Nucleotide, Brain Diseases metabolism, Genome-Wide Association Study, Nerve Tissue Proteins genetics, Receptors, Cell Surface genetics
- Abstract
Sortilin-related vacuolar protein sorting 10 ( VPS10 ) domain containing receptor 3 ( SORCS3 ) is a neuron-specific transmembrane protein involved in the trafficking of proteins between intracellular vesicles and the plasma membrane. Genetic variation at SORCS3 is associated with multiple neuropsychiatric disorders and behavioural phenotypes. Here, we undertake a systematic search of published genome-wide association studies to identify and catalogue associations between SORCS3 and brain-related disorders and traits. We also generate a SORCS3 gene-set based on protein-protein interactions and investigate the contribution of this gene-set to the heritability of these phenotypes and its overlap with synaptic biology. Analysis of association signals at SORSC3 showed individual SNPs to be associated with multiple neuropsychiatric and neurodevelopmental brain-related disorders and traits that have an impact on the experience of feeling, emotion or mood or cognitive function, while multiple LD-independent SNPs were associated with the same phenotypes. Across these SNPs, alleles associated with the more favourable outcomes for each phenotype (e.g., decreased risk of neuropsychiatric illness) were associated with increased expression of the SORCS3 gene. The SORCS3 gene-set was enriched for heritability contributing to schizophrenia (SCZ), bipolar disorder (BPD), intelligence (IQ) and education attainment (EA). Eleven genes from the SORCS3 gene-set were associated with more than one of these phenotypes at the genome-wide level, with RBFOX1 associated with SCZ, IQ and EA. Functional annotation revealed that the SORCS3 gene-set is enriched for multiple ontologies related to the structure and function of synapses. Overall, we find many independent association signals at SORCS3 with brain-related disorders and traits, with the effect possibly mediated by reduced gene expression, resulting in a negative impact on synaptic function.
- Published
- 2023
- Full Text
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34. The Lung Microbiome: A New Frontier for Lung and Brain Disease.
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Chen J, Li T, Ye C, Zhong J, Huang JD, Ke Y, and Sun H
- Subjects
- Humans, Lung, Bacteria, Lung Diseases, Microbiota, Brain Diseases
- Abstract
Due to the limitations of culture techniques, the lung in a healthy state is traditionally considered to be a sterile organ. With the development of non-culture-dependent techniques, the presence of low-biomass microbiomes in the lungs has been identified. The species of the lung microbiome are similar to those of the oral microbiome, suggesting that the microbiome is derived passively within the lungs from the oral cavity via micro-aspiration. Elimination, immigration, and relative growth within its communities all contribute to the composition of the lung microbiome. The lung microbiome is reportedly altered in many lung diseases that have not traditionally been considered infectious or microbial, and potential pathways of microbe-host crosstalk are emerging. Recent studies have shown that the lung microbiome also plays an important role in brain autoimmunity. There is a close relationship between the lungs and the brain, which can be called the lung-brain axis. However, the problem now is that it is not well understood how the lung microbiota plays a role in the disease-specifically, whether there is a causal connection between disease and the lung microbiome. The lung microbiome includes bacteria, archaea, fungi, protozoa, and viruses. However, fungi and viruses have not been fully studied compared to bacteria in the lungs. In this review, we mainly discuss the role of the lung microbiome in chronic lung diseases and, in particular, we summarize the recent progress of the lung microbiome in multiple sclerosis, as well as the lung-brain axis.
- Published
- 2023
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35. Framework to Detect Schizophrenia in Brain MRI Slices with Mayfly Algorithm-Selected Deep and Handcrafted Features.
- Author
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Manic KS, Rajinikanth V, Al-Bimani AS, Taniar D, and Kadry S
- Subjects
- Animals, Humans, Magnetic Resonance Imaging methods, Algorithms, Brain diagnostic imaging, Schizophrenia diagnostic imaging, Ephemeroptera, Brain Diseases
- Abstract
Brain abnormality causes severe human problems, and thorough screening is necessary to identify the disease. In clinics, bio-image-supported brain abnormality screening is employed mainly because of its investigative accuracy compared with bio-signal (EEG)-based practice. This research aims to develop a reliable disease screening framework for the automatic identification of schizophrenia (SCZ) conditions from brain MRI slices. This scheme consists following phases: (i) MRI slices collection and pre-processing, (ii) implementation of VGG16 to extract deep features (DF), (iii) collection of handcrafted features (HF), (iv) mayfly algorithm-supported optimal feature selection, (v) serial feature concatenation, and (vi) binary classifier execution and validation. The performance of the proposed scheme was independently tested with DF, HF, and concatenated features (DF+HF), and the achieved outcome of this study verifies that the schizophrenia screening accuracy with DF+HF is superior compared with other methods. During this work, 40 patients’ brain MRI images (20 controlled and 20 SCZ class) were considered for the investigation, and the following accuracies were achieved: DF provided >91%, HF obtained >85%, and DF+HF achieved >95%. Therefore, this framework is clinically significant, and in the future, it can be used to inspect actual patients’ brain MRI slices.
- Published
- 2022
- Full Text
- View/download PDF
36. Early Diagnosis of Brain Diseases Using Artificial Intelligence and EV Molecular Data: A Proposed Noninvasive Repeated Diagnosis Approach.
- Author
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Park JH and Moon J
- Subjects
- Humans, Biomarkers, Brain, Early Diagnosis, Artificial Intelligence, Brain Diseases diagnosis
- Abstract
Brain-derived extracellular vesicles (BDEVs) are released from the central nervous system. Brain-related research and diagnostic techniques involving BDEVs have rapidly emerged as a means of diagnosing brain disorders because they are minimally invasive and enable repeatable measurements based on body fluids. However, EVs from various cells and organs are mixed in the blood, acting as potential obstacles for brain diagnostic systems using BDEVs. Therefore, it is important to screen appropriate brain EV markers to isolate BDEVs in blood. Here, we established a strategy for screening potential BDEV biomarkers. To collect various molecular data from the BDEVs, we propose that the sensitivity and specificity of the diagnostic system could be enhanced using machine learning and AI analysis. This BDEV-based diagnostic strategy could be used to diagnose various brain diseases and will help prevent disease through early diagnosis and early treatment.
- Published
- 2022
- Full Text
- View/download PDF
37. Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia.
- Author
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Zalewska T, Pawelec P, Ziabska K, and Ziemka-Nalecz M
- Subjects
- Male, Female, Humans, Sex Characteristics, Brain, Neurodegenerative Diseases genetics, Brain Diseases, Brain Ischemia
- Abstract
Epidemiological studies and clinical observations show evidence of sexual dimorphism in brain responses to several neurological conditions. It is suggested that sex-related differences between men and women may have profound effects on disease susceptibility, pathophysiology, and progression. Sexual differences of the brain are achieved through the complex interplay of several factors contributing to this phenomenon, such as sex hormones, as well as genetic and epigenetic differences. Despite recent advances, the precise link between these factors and brain disorders is incompletely understood. This review aims to briefly outline the most relevant aspects that differ between men and women in ischemia and neurodegenerative disorders (AD, PD, HD, ALS, and SM). Recognition of disparities between both sexes could aid the development of individual approaches to ameliorate or slow the progression of intractable disorders., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
- Published
- 2022
- Full Text
- View/download PDF
38. Pathogenesis and Preventive Tactics of Immune-Mediated Non-Pulmonary COVID-19 in Children and Beyond.
- Author
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Chi H, Chang L, Chao YC, Lin DS, Yang HW, Fang LC, Lin CH, Ho CS, and Yang KD
- Subjects
- Adult, Child, Aged, Humans, Pandemics, COVID-19, Brain Diseases
- Abstract
The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.
- Published
- 2022
- Full Text
- View/download PDF
39. The Role of Copper Homeostasis in Brain Disease.
- Author
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An Y, Li S, Huang X, Chen X, Shan H, and Zhang M
- Subjects
- Humans, Central Nervous System, Brain, Homeostasis, Copper, Brain Diseases
- Abstract
In the human body, copper is an important trace element and is a cofactor for several important enzymes involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis, and neurotransmitter synthesis. Copper is also necessary for cellular processes, such as the regulation of intracellular signal transduction, catecholamine balance, myelination of neurons, and efficient synaptic transmission in the central nervous system. Copper is naturally present in some foods and is available as a dietary supplement. Only small amounts of copper are typically stored in the body and a large amount of copper is excreted through bile and urine. Given the critical role of copper in a breadth of cellular processes, local concentrations of copper and the cellular distribution of copper transporter proteins in the brain are important to maintain the steady state of the internal environment. The dysfunction of copper metabolism or regulatory pathways results in an imbalance in copper homeostasis in the brain, which can lead to a myriad of acute and chronic pathological effects on neurological function. It suggests a unique mechanism linking copper homeostasis and neuronal activation within the central nervous system. This article explores the relationship between impaired copper homeostasis and neuropathophysiological progress in brain diseases.
- Published
- 2022
- Full Text
- View/download PDF
40. Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.
- Author
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Ren ZL, Li CX, Ma CY, Chen D, Chen JH, Xu WX, Chen CA, Cheng FF, and Wang XQ
- Subjects
- Humans, Receptors, G-Protein-Coupled metabolism, Bile Acids and Salts metabolism, Signal Transduction, Liver metabolism, Fibroblast Growth Factors metabolism, Non-alcoholic Fatty Liver Disease metabolism, Brain Diseases metabolism
- Abstract
A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.
- Published
- 2022
- Full Text
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41. A Complex Genomic Rearrangement Resulting in Loss of Function of SCN1A and SCN2A in a Patient with Severe Developmental and Epileptic Encephalopathy.
- Author
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Orlando V, Di Tommaso S, Alesi V, Loddo S, Genovese S, Catino G, Martucci L, Roberti MC, Trivisano M, Dentici ML, Specchio N, Dallapiccola B, Ferretti A, and Novelli A
- Subjects
- Humans, Karyotyping, Translocation, Genetic, Chromosome Inversion, Karyotype, Genomics, NAV1.2 Voltage-Gated Sodium Channel genetics, NAV1.1 Voltage-Gated Sodium Channel, Chromosome Aberrations, Brain Diseases
- Abstract
Complex genomic rearrangements (CGRs) are structural variants arising from two or more chromosomal breaks, which are challenging to characterize by conventional or molecular cytogenetic analysis (karyotype and FISH). The integrated approach of standard and genomic techniques, including optical genome mapping (OGM) and genome sequencing, is crucial for disclosing and characterizing cryptic chromosomal rearrangements at high resolutions. We report on a patient with a complex developmental and epileptic encephalopathy in which karyotype analysis showed a de novo balanced translocation involving the long arms of chromosomes 2 and 18. Microarray analysis detected a 194 Kb microdeletion at 2q24.3 involving the SCN2A gene, which was considered the likely translocation breakpoint on chromosome 2. However, OGM redefined the translocation breakpoints by disclosing a paracentric inversion at 2q24.3 disrupting SCN1A . This combined genomic high-resolution approach allowed a fine characterization of the CGR, which involves two different chromosomes with four breakpoints. The patient's phenotype resulted from the concomitant loss of function of SCN1A and SCN2A .
- Published
- 2022
- Full Text
- View/download PDF
42. Knowledge-Based Remote E-Coaching Framework Using IoT Devices for In-Home ADL Rehabilitation Treatment of Degenerative Brain Disease Patients.
- Author
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Kim HJ, Jeong SY, and Kang SJ
- Subjects
- Humans, Aged, Activities of Daily Living, Wireless Technology, Technology, Mentoring, Brain Diseases
- Abstract
The activities of daily living (ADL) ability level of an elderly patient is an important indicator in determining the patient's degree of degenerative brain disease and is mainly evaluated through face-to-face interviews with doctors and patients in hospitals. It is impossible to determine the exact ADL ability of a patient through such a temporary interview, and the pursuit of accurate ADL ability evaluation technology is a very important research task worldwide. In this paper, in order to overcome the limitations of the existing ADL evaluation method mentioned above, first of all, a self-organized IoT architecture in which IoT devices autonomously and non-invasively measure a patient's ADL ability within the context of the patient's daily living place was designed and implemented. Second, a remote rehabilitation treatment concept for enhancing the patient's ADL ability we call an "e-coaching framework", in which a doctor remotely gives an instruction in a specific ADL scenario, and the patient's ability to understand and perform the instruction can be measured on-line and in real time, was additionally developed on top of the self-organized IoT architecture. In order to verify the possibility of remote rehabilitation treatment through the proposed architecture, various remotely directed ADL scenarios were performed and the accuracy of the measurements was verified.
- Published
- 2022
- Full Text
- View/download PDF
43. Molybdenum Cofactor Deficiency in Humans.
- Author
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Johannes L, Fu CY, and Schwarz G
- Subjects
- Male, Infant, Newborn, Humans, Cysteine, Thiosulfates, Cystine, Coenzymes metabolism, Sulfites, Molybdenum Cofactors, Molybdenum, Metalloproteins metabolism, Sulfite Oxidase genetics, Brain Diseases
- Abstract
Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic-ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1 , MOCS2, MOCS3, and GPHN . Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.
- Published
- 2022
- Full Text
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44. A Novel Homozygous Founder Variant of RTN4IP1 in Two Consanguineous Saudi Families.
- Author
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Aldosary M, Alsagob M, AlQudairy H, González-Álvarez AC, Arold ST, Dababo MA, Alharbi OA, Almass R, AlBakheet A, AlSarar D, Qari A, Al-Ansari MM, Oláhová M, Al-Shahrani SA, AlSayed M, Colak D, Taylor RW, AlOwain M, and Kaya N
- Subjects
- Antioxidants, Carrier Proteins genetics, Humans, Mitochondrial Proteins genetics, Mutation genetics, NADP genetics, Oxidoreductases genetics, Saudi Arabia, Brain Diseases, Optic Atrophy genetics
- Abstract
The genetic architecture of mitochondrial disease continues to expand and currently exceeds more than 350 disease-causing genes. Bi-allelic variants in RTN4IP1 , also known as Optic Atrophy-10 (OPA10), lead to early-onset recessive optic neuropathy, atrophy, and encephalopathy in the afflicted patients. The gene is known to encode a mitochondrial ubiquinol oxidoreductase that interacts with reticulon 4 and is thought to be a mitochondrial antioxidant NADPH oxidoreductase. Here, we describe two unrelated consanguineous families from the northern region of Saudi Arabia harboring a missense variant ( RTN4IP1 :NM_032730.5; c.475G
- Published
- 2022
- Full Text
- View/download PDF
45. Hashimoto Encephalopathy-Still More Questions than Answers.
- Author
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Waliszewska-Prosół M and Ejma M
- Subjects
- Hormones, Humans, Brain Diseases, Hashimoto Disease diagnosis, Hashimoto Disease etiology, Hashimoto Disease pathology
- Abstract
The normal function of the nervous system is conditioned by the undisturbed function of the thyroid gland and its hormones. Comprehensive clinical manifestations, including neurological disorders in Hashimoto's thyroiditis, have long been understood and, in recent years, attention has been paid to neurological symptoms in euthyroid patients. Hashimoto encephalopathy is a controversial and poorly understood disease entity and the pathogenesis of the condition remains unclear. We still derive our understanding of this condition from case reports, but on the basis of these, a clear clinical picture of this entity can be proposed. Based on a review of the recent literature, the authors present the current view on the subject, discuss controversies and questions that still remain unanswered, as well as ongoing research in this area and the results of our own work in patients with Hashimoto's thyroiditis.
- Published
- 2022
- Full Text
- View/download PDF
46. Variable Expression of GABAA Receptor Subunit Gamma 2 Mutation in a Nuclear Family Displaying Developmental and Encephalopathic Phenotype.
- Author
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Nwosu G, Reddy SB, Riordan HRM, and Kang JQ
- Subjects
- Humans, Mutation, Nuclear Family, Phenotype, Quality of Life, Brain Diseases, Receptors, GABA-A genetics, Receptors, GABA-A metabolism
- Abstract
Mutations in GABA
A receptor subunit genes ( GABRs ) are a major etiology for developmental and epileptic encephalopathies (DEEs). This article reports a case of a genetic abnormality in GABRG2 and updates the pathophysiology and treatment development for mutations in DEEs based on recent advances. Mutations in GABRs , especially in GABRA1 , GABRB2 , GABRB3 , and GABRG2 , impair GABAergic signaling and are frequently associated with DEEs such as Dravet syndrome and Lennox-Gastaut syndrome, as GABAergic signaling is critical for early brain development. We here present a novel association of a microdeletion of GABRG2 with a diagnosed DEE phenotype. We characterized the clinical phenotype and underlying mechanisms, including molecular genetics, EEGs, and MRI. We then compiled an update of molecular mechanisms of GABR mutations, especially the mutations in GABRB3 and GABRG2 attributed to DEEs. Genetic therapy is also discussed as a new avenue for treatment of DEEs through employing antisense oligonucleotide techniques. There is an urgent need to define treatment targets and explore new treatment paradigms for the DEEs, as early deployment could alleviate long-term disabilities and improve quality of life for patients. This study highlights biomolecular targets for future therapeutic interventions, including via both pharmacological and genetic approaches.- Published
- 2022
- Full Text
- View/download PDF
47. Nanobiotechnology: A New Frontier for Brain Disorders.
- Author
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Picone P
- Subjects
- Humans, Brain Diseases, Neurodegenerative Diseases
- Abstract
Brain disorders, such as neurodegenerative diseases (NDs) and tumors (more than 600 pathologies), are a serious health problem, resulting in brain dysfunctions that limit normal activities, with a significant economic impact [...].
- Published
- 2022
- Full Text
- View/download PDF
48. Reversible Splenial Lesion Syndrome as a Challenging Casuistry.
- Author
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Tatar D, Bocian B, Świerzy K, and Badura Brzoza K
- Subjects
- Adult, Casuistry, Corpus Callosum diagnostic imaging, Corpus Callosum pathology, Diffusion Magnetic Resonance Imaging adverse effects, Humans, Magnetic Resonance Imaging adverse effects, Syndrome, Young Adult, Brain Diseases diagnosis
- Abstract
The corpus callosum plays a vital role in brain function. In particular, in the trunk of the corpus callosum, in the course of various diseases, there may be temporary, reversible changes (reversible splenial lesion syndrome (RESLES)), as well as partially reversible and irreversible changes. This article discusses the differentiation of RESLES and other conditions with changes in the corpus callosum lobe, as well as the accompanying clinical symptoms. Moreover, a case report of a patient in whom the above changes appeared in the nuclear magnetic resonance (NMR) image is presented. A 20-year-old patient with the diagnosis of Ehlers-Danlos syndrome type VI was admitted to the psychiatric ward in an emergency because of psychomotor agitation, refusal to take food and fluids, delusional statements with a message, grandeur, and auditory hallucinations. In the performed magnetic resonance imaging (MRI) of the brain, the corpus callosum non-characteristic in T2-weighted images revealed a hyperintensive area, which was significantly hyperintensive in diffusion magnetic resonance (DWI) sequences and in apparent diffusion coefficient (ADC) sequences with reduced signal intensity and no signs of bleeding. The hypothesis of subacute ischemic stroke of the corpus callosum was presented. In the control MRI of the brain, changes in the corpus callosum completely regressed, thus excluding an ischemic etiology and favoring the diagnosis of RESLES. During hospitalization, the patient experienced significant fluctuations in mental status, with the dominant symptoms typical of the paranoid syndrome in the form of disturbances in the course and structure of thinking and perception, and a clear and stable improvement was obtained after the administration of long-acting intramuscular olanzapine. Taking into account the clinical and radiological picture, the age of the episode, the rapidity of the disease development, the persistence of its clinical symptoms after the withdrawal of radiological changes in the brain NMR image, as well as the significant improvement in the clinical condition after the introduction of antipsychotic drugs, the final diagnosis was made of schizophrenia.
- Published
- 2022
- Full Text
- View/download PDF
49. Effect of 3D Synthetic Microscaffold Nichoid on the Morphology of Cultured Hippocampal Neurons and Astrocytes.
- Author
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Musi CA, Colnaghi L, Giani A, Priori EC, Marchini G, Tironi M, Conci C, Cerullo G, Osellame R, Raimondi MT, Remuzzi A, and Borsello T
- Subjects
- Coculture Techniques, Hippocampus, Humans, Neurons metabolism, Astrocytes, Brain Diseases metabolism
- Abstract
The human brain is the most complex organ in biology. This complexity is due to the number and the intricate connections of brain cells and has so far limited the development of in vitro models for basic and applied brain research. We decided to create a new, reliable, and cost-effective in vitro system based on the Nichoid, a 3D microscaffold microfabricated by two-photon laser polymerization technology. We investigated whether these 3D microscaffold devices can create an environment allowing the manipulation, monitoring, and functional assessment of a mixed population of brain cells in vitro. With this aim, we set up a new model of hippocampal neurons and astrocytes co-cultured in the Nichoid microscaffold to generate brain micro-tissues of 30 μm thickness. After 21 days in culture, we morphologically characterized the 3D spatial organization of the hippocampal astrocytes and neurons within the microscaffold, and we compared our observations to those made using the classical 2D co-culture system. We found that the co-cultured cells colonized the entire volume of the 3D devices. Using confocal microscopy, we observed that within this period the different cell types had become well-differentiated. This was further elaborated with the use of drebrin, PSD-95, and synaptophysin antibodies that labeled the majority of neurons, both in the 2D as well as in the 3D co-cultures. Using scanning electron microscopy, we found that neurons in the 3D co-culture displayed a significantly larger amount of dendritic protrusions compared to neurons in the 2D co-culture. This latter observation indicates that neurons growing in a 3D environment may be more prone to form connections than those co-cultured in a 2D condition. Our results show that the Nichoid can be used as a 3D device to investigate the structure and morphology of neurons and astrocytes in vitro. In the future, this model can be used as a tool to study brain cell interactions in the discovery of important mechanisms governing neuronal plasticity and to determine the factors that form the basis of different human brain diseases. This system may potentially be further used for drug screening in the context of various brain diseases.
- Published
- 2022
- Full Text
- View/download PDF
50. Role of Seipin in Human Diseases and Experimental Animal Models.
- Author
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Li Y, Yang X, Peng L, Xia Q, Zhang Y, Huang W, Liu T, and Jia D
- Subjects
- Animals, Humans, Models, Animal, Brain Diseases, GTP-Binding Protein gamma Subunits genetics, GTP-Binding Protein gamma Subunits metabolism, Lipodystrophy genetics, Lipodystrophy, Congenital Generalized genetics, Lipodystrophy, Congenital Generalized metabolism
- Abstract
Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 ( BSCL2 ) gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). BSCL2 gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and BSCL2 -associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. In the current study, we comprehensively summarise phenotypes, underlying mechanisms, and treatment of human diseases caused by BSCL2 gene mutations, paralleled by animal studies including systemic or specific Bscl2 gene knockout, or Bscl2 gene overexpression. In various animal models representing diseases that are not related to Bscl2 mutations, differential expression patterns and functional roles of seipin are also described. Furthermore, we highlight the potential therapeutic approaches by targeting seipin or its upstream and downstream signalling pathways. Taken together, restoring adipose tissue function and targeting seipin-related pathways are effective strategies for CGL2 treatment. Meanwhile, seipin-related pathways are also considered to have potential therapeutic value in diseases that are not caused by BSCL2 gene mutations.
- Published
- 2022
- Full Text
- View/download PDF
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