Molecular Psychiatry, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 7, 2024
Язык: Английский
Molecular Psychiatry, Год журнала: 2024, Номер 29(9), С. 2821 - 2833
Опубликована: Март 29, 2024
In the brain, astrocytes regulate shape and functions of synaptic vascular compartments through a variety released factors membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to onset severe pathologies. Clinical pre-clinical studies show alterations in cell number, morphology, molecular makeup astrocyte-dependent processes different affected regions neurodevelopmental (ND) neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate mature during critical period early postnatal time window elevated glia-dependent regulation proper balance between synapse formation/elimination, which is pivotal refining connectivity. Therefore, any intrinsic and/or extrinsic altering these may result an aberrant remodeling mental The peculiar bridging position further allows them "compute" state consequently secrete bloodstream, serve as diagnostic biomarkers distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis astrocyte-mediated neuronal network periods focusing elimination. We then propose alternative hypotheses for involvement aberrancies ND NP light well-known differential prevalence certain disorders males females, also discuss putative sex-dependent influences events. From translational perspective, understanding age- astrocyte-specific functional changes help identify cellular (dys)functions health disease, favouring development tools selection tailored treatment options male/female patients.
Язык: Английский
Процитировано
26
NeuroImage, Год журнала: 2024, Номер 289, С. 120551 - 120551
Опубликована: Фев. 20, 2024
It has been revealed that abnormal voxel-mirrored homotopic connectivity (VMHC) is present in patients with schizophrenia, yet there are inconsistencies the relevant findings. Moreover, little known about their association brain gene expression profiles. In this study, transcription-neuroimaging analyses using data from Allen Human Brain Atlas and case-control VMHC differences both discovery (meta-analysis, including 9 studies a total of 386 357 controls) replication (separate group-level comparisons within two datasets, 258 287 phases were performed to identify genes associated alterations. Enrichment conducted characterize biological functions specific identified genes, Neurosynth decoding analysis was examine correlation between cognitive-related processes alterations schizophrenia. phases, schizophrenia exhibited consistent changes compared controls, which correlated series processes; meta-regression illness duration negatively abnormalities cerebellum postcentral/precentral gyrus. The patterns stably 1287 enriched for fundamental like regulation cell communication, nervous system development, communication. addition, these overexpressed astrocytes immune cells, extensive cortical regions wide developmental time windows. findings may contribute more comprehensive understanding molecular mechanisms underlying
Язык: Английский
Процитировано
19
Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2022, Номер 120, С. 110626 - 110626
Опубликована: Авг. 31, 2022
Язык: Английский
Процитировано
59
Glia, Год журнала: 2022, Номер 70(9), С. 1585 - 1604
Опубликована: Май 30, 2022
Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, precise etiology still poorly understood. not characterized by gross pathology, but involves subtle pathological changes in neuronal populations glial cells. Among the latter, astrocytes critically contribute to regulation of neurodevelopmental processes, any dysfunctions their morphological functional maturation may lead aberrant processes involved pathogenesis schizophrenia, such as mitochondrial biogenesis, synaptogenesis, glutamatergic dopaminergic transmission. Studies mechanisms regulating astrocyte therefore improve our understanding cellular molecular underlying schizophrenia.
Язык: Английский
Процитировано
52
Neuronal Signaling, Год журнала: 2023, Номер 7(2)
Опубликована: Май 17, 2023
Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence support these mechanistic links, with placental inflammatory responses dysregulation function implicated. This leads changes in fetal brain balance altered epigenetic regulation key pathways. The prenatal timing such mIA-evoked changes, accompanying developmental an
Язык: Английский
Процитировано
27
Brain Behavior and Immunity, Год журнала: 2023, Номер 113, С. 415 - 431
Опубликована: Авг. 3, 2023
The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity TSPO to identify brain processes appears vary greatly across disorders, disease stages, applied quantification methods. To advance potential biomarker evaluate inflammation anti-inflammatory therapies, better understanding its applicability disorders needed. We conducted transdiagnostic systematic review meta-analysis all vivo human case-control studies CNS. Specifically, we investigated direction, strength, heterogeneity associated with signal pre-specified regions, explored demographic methodological sources heterogeneity.We searched English peer-reviewed articles that differences. extracted details, outcomes, technical variables procedure. A random-effects was estimate standardized mean differences (SMD) lobar/whole-brain cortical grey matter (cGM), thalamus, cortico-limbic circuitry between different illness categories. Heterogeneity evaluated I2 statistic using subgroup meta-regression analyses radioligand generation, method, age, sex, publication year. Significance set at False Discovery Rate (FDR)-corrected P < 0.05.156 individual were included review, incorporating data 2381 healthy controls 2626 patients. 139 documented meta-analysable grouped into 11 Across categories, observed significantly higher cases compared cGM (n = 121 studies, SMD 0.358, PFDR 0.001, 68%), significant difference categories (P 0.004). increases only Alzheimer's (SMD 0.693, 64%) other neurodegenerative 0.929, 73%). Cortico-limbic 97 0.541, 67%) most prominent disease, mild cognitive impairment, mood multiple sclerosis. Thalamic involvement 79 0.393, 71%) sclerosis, chronic pain functional (all 0.05). Main outcomes systemic immunological viral infections, substance use schizophrenia traumatic injury not significant. identified between-study variance including strong effect method (explaining 25% variance; VT-based 0.000 versus reference tissue-based 0.630; F 20.49, df 1;103, 0.001), patient age (9% variance), generation (5% variance).This study first overarching findings humans several regions. robust specific types which widespread or focal depending on category. also found large horizontal (positive) shift estimates studies. Our results can support future optimize experimental design power calculations, by taking account type disorder, region-of-interest, radioligand, method.
Язык: Английский
Процитировано
27
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1250 - 1250
Опубликована: Янв. 19, 2024
Schizophrenia (SCZ) is an articulated psychiatric syndrome characterized by a combination of genetic, epigenetic, and environmental factors. Our intention to present pathogenetic model combining SCZ alterations the main cellular actors blood-brain barrier (BBB): endothelial cells (ECs), pericytes, astrocytes. The homeostasis BBB preserved neurovascular unit which constituted ECs, astrocytes microglia, neurons, extracellular matrix. role strictly linked its ability preserve biochemical integrity brain parenchyma integrity. In SCZ, there increased permeability, demonstrated elevated levels albumin immunoglobulins in cerebrospinal fluid, this result intrinsic impairment. Increased permeability would lead enhanced concentrations neurotoxic neuroactive molecules brain. involvement reverberates consequences on BBB, together with impact selectivity represented EC pericyte damage occurring psychotic picture. Understanding strict interaction between ECs astrocytes, consequent cognition, diriment not only for comprehension neurotransmitter dyshomeostasis but also focusing other potential therapeutic targets.
Язык: Английский
Процитировано
8
Glia, Год журнала: 2023, Номер 71(7), С. 1667 - 1682
Опубликована: Март 22, 2023
Abstract Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis regulating synaptic transmission, the sum which results in behavior modulation. These interactions possible due their complex morphology, composed a tree‐like structure processes cover defined territories ramifying mesh‐like system fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention dynamic with synapses, our knowledge about “backbone” physiological conditions is incomplete. Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity regions such as hippocampus, crucial for cognitive emotional behaviors. In this study, we carried out analysis astrocytes across hippocampal subfields Cornu Ammonis area 1 (CA1) dentate gyrus dorsoventral axis. We found that display subfields, conserved along further appear contribute an exocytosis‐dependent manner signaling loop maintains backbone structure. findings reveal appears follow layer‐specific cues depend on neuro‐glial environment.
Язык: Английский
Процитировано
21
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10762 - 10762
Опубликована: Июнь 28, 2023
Understanding the complexities of human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations replicating intricacies, necessitating development vitro models that can simulate structure function. Three-dimensional models, including organoids, cerebral bioprinted functionalized offer promising platforms for studying development, physiology, disease. These accurately replicate key aspects anatomy, gene expression, cellular behavior, enabling drug discovery toxicology studies while providing insights into human-specific phenomena not easily studied animal models. The use human-induced pluripotent stem cells has revolutionized generation 3D structures, with various techniques developed to generate specific regions. advancements facilitate study function, overcoming previous due scarcity samples. This technical review provides an overview current cortex, their characterization, limitations, explores state art future directions field, focus on applications neurodevelopmental neurodegenerative disorders.
Язык: Английский
Процитировано
19
Biomolecules, Год журнала: 2024, Номер 14(10), С. 1204 - 1204
Опубликована: Сен. 25, 2024
Astrocytes are one of the key glial types central nervous system (CNS), accounting for over 20% total cells in brain. Extensive evidence has established their indispensable functions maintenance CNS homeostasis, as well broad involvement neurological conditions. In particular, astrocytes can participate various neuroinflammatory processes, e.g., releasing a repertoire cytokines and chemokines or specific neurotrophic factors, which result both beneficial detrimental effects. It become increasingly clear that such astrocyte-mediated neuroinflammation, together with its complex crosstalk other immune cells, designates neuronal survival functional integrity neurocircuits, thus critically contributing to disease onset progression. this review, we focus on current knowledge responses astrocytes, summarizing common features Moreover, highlight several vital questions future research promise novel insights into diagnostic therapeutic strategies against those debilitating diseases.
Язык: Английский
Процитировано
7