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Neuropsychopharmacology : Official... Jan 2017
Topics: Animals; Autism Spectrum Disorder; Brain; Brain Diseases; Humans; Immune System; Mental Disorders; Neurodegenerative Diseases; Schizophrenia; Stress, Psychological
PubMed: 27909328
DOI: 10.1038/npp.2016.229 -
Molecules and Cells Sep 2019Brain organoids are an exciting new technology with the potential to significantly change our understanding of the development and disorders of the human brain. With... (Review)
Review
Brain organoids are an exciting new technology with the potential to significantly change our understanding of the development and disorders of the human brain. With step-by-step differentiation protocols, three-dimensional neural tissues are self-organized from pluripotent stem cells, and recapitulate the major millstones of human brain development in vitro. Recent studies have shown that brain organoids can mimic the spatiotemporal dynamicity of neurogenesis, the formation of regional neural circuitry, and the integration of glial cells into a neural network. This suggests that brain organoids could serve as a representative model system to study the human brain. In this review, we will overview the development of brain organoid technology, its current progress and applications, and future prospects of this technology.
Topics: Brain; Brain Diseases; Humans; Organoids; Tissue Engineering
PubMed: 31564073
DOI: 10.14348/molcells.2019.0162 -
The Journal of Head Trauma... 2019Mild traumatic brain injury (mTBI) is a major public health concern that has generated considerable scientific interest as a complex brain disorder that is associated... (Review)
Review
OBJECTIVES
Mild traumatic brain injury (mTBI) is a major public health concern that has generated considerable scientific interest as a complex brain disorder that is associated with long-term neural consequences. This article reviews the literature on cerebrovascular dysfunction in chronic mTBI, with a focus on the long-term neural implications of such dysfunction.
METHODS AND RESULTS
Evidence is presented from human neuroimaging studies to support cerebrovascular involvement in long-term mTBI pathology. In addition, a pathway between mTBI and neurodegeneration via cerebrovascular dysfunction is explored.
CONCLUSIONS
Future work focused on identifying the neurobiological mechanisms underlying the neural consequences of mTBI will be important to guide therapeutic interventions and long-term care for patients with mTBI.
Topics: Brain Concussion; Cerebrovascular Disorders; Chronic Disease; Humans; Neurodegenerative Diseases
PubMed: 30499930
DOI: 10.1097/HTR.0000000000000449 -
Dialogues in Clinical Neuroscience Dec 2016The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the...
The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.
Topics: Brain Diseases; Female; Gender Identity; Humans; Male; Mental Disorders; Risk Factors; Sex Characteristics; Sex Factors
PubMed: 28179806
DOI: 10.31887/DCNS.2016.18.4/fthibaut -
Journal of Neural Transmission (Vienna,... Aug 2023Depression is frequent in older individuals and is often associated with cognitive impairment and increasing risk of subsequent dementia. Late-life depression (LLD) has... (Review)
Review
Depression is frequent in older individuals and is often associated with cognitive impairment and increasing risk of subsequent dementia. Late-life depression (LLD) has a negative impact on quality of life, yet the underlying pathobiology is still poorly understood. It is characterized by considerable heterogeneity in clinical manifestation, genetics, brain morphology, and function. Although its diagnosis is based on standard criteria, due to overlap with other age-related pathologies, the relationship between depression and dementia and the relevant structural and functional cerebral lesions are still controversial. LLD has been related to a variety of pathogenic mechanisms associated with the underlying age-related neurodegenerative and cerebrovascular processes. In addition to biochemical abnormalities, involving serotonergic and GABAergic systems, widespread disturbances of cortico-limbic, cortico-subcortical, and other essential brain networks, with disruption in the topological organization of mood- and cognition-related or other global connections are involved. Most recent lesion mapping has identified an altered network architecture with "depressive circuits" and "resilience tracts", thus confirming that depression is a brain network dysfunction disorder. Further pathogenic mechanisms including neuroinflammation, neuroimmune dysregulation, oxidative stress, neurotrophic and other pathogenic factors, such as β-amyloid (and tau) deposition are in discussion. Antidepressant therapies induce various changes in brain structure and function. Better insights into the complex pathobiology of LLD and new biomarkers will allow earlier and better diagnosis of this frequent and disabling psychopathological disorder, and further elucidation of its complex pathobiological basis is warranted in order to provide better prevention and treatment of depression in older individuals.
Topics: Humans; Aged; Depression; Cognition Disorders; Quality of Life; Brain; Brain Diseases; Cognitive Dysfunction; Dementia
PubMed: 37145167
DOI: 10.1007/s00702-023-02648-z -
Revista de Neurologia Jun 2018Thanks to the application of modern techniques such as next-generation sequencing in the study of apparently non-inherited encephalopathies it has become possible to...
Thanks to the application of modern techniques such as next-generation sequencing in the study of apparently non-inherited encephalopathies it has become possible to describe de novo pathogenic mutations in unsuspected genes and to define the phenotypes of these mutations. Interestingly, in most cases, their clinical signs and symptoms show a spectrum in which epileptic encephalopathy, neurodevelopmental disorder and hyperkinetic abnormal movement disorders overlap. Their pathophysiology is located in synapses (synaptopathies). This article offers a brief summary of these disorders and also includes a simple note, in honour of Dr Natalio Fejerman (1934-2018), on the so-called «benign polymorphic disorder of infancy».
Topics: Brain Diseases; Humans; Movement Disorders; Nervous System Diseases; Synapses
PubMed: 29876907
DOI: No ID Found -
The Journal of Neuroscience : the... Nov 2014The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases... (Review)
Review
The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.
Topics: Animals; Anti-Bacterial Agents; Brain; Brain Diseases; Gastrointestinal Tract; Humans; Microbiota; Probiotics
PubMed: 25392516
DOI: 10.1523/JNEUROSCI.3299-14.2014 -
International Journal of Molecular... Jun 2023Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia... (Review)
Review
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 (, , , and ) and three recessive inherited genes (, , and ). 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.
Topics: Humans; Brain Diseases; Basal Ganglia Diseases; Brain; Phenotype; Proto-Oncogene Proteins c-sis; Mutation; Sodium-Phosphate Cotransporter Proteins, Type III
PubMed: 37446066
DOI: 10.3390/ijms241310886 -
Neuroscience Bulletin Apr 2023Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,... (Review)
Review
Primary familial brain calcification (PFBC) is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain, accompanied by various symptoms, such as dystonia, ataxia, parkinsonism, dementia, depression, headaches, and epilepsy. Currently, the etiology of PFBC is largely unknown, and no specific prevention or treatment is available. During the past 10 years, six causative genes (SLC20A2, PDGFRB, PDGFB, XPR1, MYORG, and JAM2) have been identified in PFBC. In this review, considering mechanistic studies of these genes at the cellular level and in animals, we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients. Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics, provides a summary of the known composition of brain calcification, and identifies some potential therapeutic targets for PFBC.
Topics: Animals; Brain Diseases; Xenotropic and Polytropic Retrovirus Receptor; Brain
PubMed: 36469195
DOI: 10.1007/s12264-022-00980-0 -
Developmental Dynamics : An Official... Jan 2019Brain organoids are an exciting new technology with the potential to significantly change how diseases of the brain are understood and treated. These three-dimensional... (Review)
Review
Brain organoids are an exciting new technology with the potential to significantly change how diseases of the brain are understood and treated. These three-dimensional neural tissues are derived from the self-organization of pluripotent stem cells, and they recapitulate the developmental process of the human brain, including progenitor zones and rudimentary cortical layers. Brain organoids have been valuable in investigating different aspects of developmental neurobiology and comparative biology. Several characteristics of organoids also make them attractive as models of brain disorders. Data generated from human organoids are more generalizable to patients because of the match in species background. Personalized organoids also can be generated from patient-derived induced pluripotent stem cells. Furthermore, the three-dimensionality of brain organoids supports cellular, mechanical, and topographical cues that are lacking in planar systems. In this review, we discuss the translational potential of brain organoids, using the examples of Zika virus, autism-spectrum disorder, and glioblastoma multiforme to consider how they could contribute to disease modeling, personalized medicine, and testing of therapeutics. We then discuss areas of improvement in organoid technology that will enhance the translational potential of brain organoids, as well as the possibility of their use as substrates for repairing cerebral circuitry after injury. Developmental Dynamics 248:53-64, 2019. © 2018 Wiley Periodicals, Inc.
Topics: Animals; Brain; Brain Diseases; Humans; Models, Biological; Organoids; Pluripotent Stem Cells; Translational Research, Biomedical
PubMed: 30091290
DOI: 10.1002/dvdy.24662