Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(6), P. 3326 - 3336

Published: Jan. 23, 2020

Significance Thirty to fifty percent of depressed individuals are unresponsive commonly prescribed antidepressant treatments, suggesting that biological mechanisms, such as stress-induced inflammation and blood vessel dysfunction, remain untreated. The blood–brain barrier is the ultimate frontier between brain harmful toxins or inflammatory signals circulating in blood. Depression vulnerability chronic social stress associated with loss this integrity; however, mechanisms involved poorly understood. Identification adaptations leading resilience under stressful conditions could help develop novel treatments. Here we combined behavioral, pharmacological, cell-specific gene profiling experiments mice epigenetic, molecular, anatomical analysis human samples unravel therapeutic potential protect promote resilience.

Language: Английский

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Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 445 - 465

Published: April 19, 2021

Language: Английский

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Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: March 21, 2019

Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most the affected patients. This unfavorable course associated multiple episodes and residual symptoms, mainly negative cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on pre-existing vulnerability thus triggers schizophrenia. Childhood trauma form renders individuals more vulnerable to developing schizophrenia; neurobiological effects such endocrine system epigenetic mechanisms are discussed. impaired working memory, executive function, verbal learning, attention schizophrenia patients, including those at ultra-high risk develop psychosis. In these higher levels childhood were correlated attenuated positive general depressive symptoms; lower global functioning; poorer performance visual episodic memory end functions. this review, we discuss specific gene variants interact patients describe new findings brain structural functional level. Additive between brain-derived neurotrophic factor methionine carriers volume loss hippocampal subregions cornu ammonis (CA)4/dentate gyrus CA2/3 have been reported A magnetic resonance imaging study showed exposure resulted aberrant function parietal areas involved cortical attention. theory mind task reflecting social cognition, was activation posterior cingulate gyrus, precuneus, dorsomedial prefrontal cortex addition, decreased connectivity shown cingulate/precuneus region amygdala high physical neglect sexual abuse during childhood, suggesting disturbances networks underlie abilities. Finally, some questionnaires commonly used assess outline possibilities use recent biostatistical methods, as machine analyze resulting datasets.

Language: Английский

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Epigenetic Modifications in Schizophrenia and Related Disorders: Molecular Scars of Environmental Exposures and Source of Phenotypic Variability

Biological Psychiatry, Journal Year: 2020, Volume and Issue: 89(3), P. 215 - 226

Published: March 28, 2020

Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia other psychiatric disorders with developmental origins. Here, we summarize clinical preclinical findings epigenetic alterations relevant disease models discuss their putative origin. Recent suggest that certain risk loci can influence stochastic variation gene expression through processes, highlighting intricate interaction between genetic control neurodevelopmental trajectories. In addition, substantial portion related may be acquired environmental factors manifested as molecular "scars." Some these scars brain functions throughout entire lifespan even transmitted across generations via germline inheritance. modifications, whether caused by or factors, plausible sources phenotypic heterogeneity offer target for therapeutic interventions. The further elucidation thus increase our knowledge regarding schizophrenia's heterogeneous and, long term, advance personalized treatments use biomarker-guided

Language: Английский

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The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(2), P. 86 - 103

Published: Dec. 10, 2021

Language: Английский

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Androgens increase excitatory neurogenic potential in human brain organoids

Nature, Journal Year: 2022, Volume and Issue: 602(7895), P. 112 - 116

Published: Jan. 19, 2022

Language: Английский

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Role of histone deacetylases and their inhibitors in neurological diseases

Pharmacological Research, Journal Year: 2024, Volume and Issue: unknown, P. 107410 - 107410

Published: Sept. 1, 2024

Histone deacetylases (HDACs) are zinc-dependent that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo vitro studies have amply demonstrated the critical role HDACs cell biology nervous system during both physiological pathological processes provided new insights into conduct research on neurological disease targets. In addition, HDAC inhibitors show promise treatment various diseases. This review summarizes regulatory mechanisms important its downstream targets diseases, therapeutic efficacy Additionally, current pharmacological situation, problems, developmental prospects described. A better understanding pathogenic may reveal interventions diseases help to relieve healthcare pressure through preventive measures.

Language: Английский

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GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Acta Pharmacologica Sinica, Journal Year: 2018, Volume and Issue: 39(5), P. 733 - 753

Published: March 22, 2018

Language: Английский

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The role of the gut microbiome in the development of schizophrenia

Schizophrenia Research, Journal Year: 2020, Volume and Issue: 234, P. 4 - 23

Published: April 23, 2020

Schizophrenia is a heterogeneous neurodevelopmental disorder involving the convergence of complex and dynamic bidirectional interaction genetic expression accumulation prenatal postnatal environmental risk factors. The development neural circuitry underlying social, cognitive emotional domains requires precise regulation from molecular signalling pathways, especially during critical periods or "windows", when brain particularly sensitive to influence input signalling. Many regions involved, substrates sub-serving these are responsive life-long microbiota-gut-brain (MGB) axis This intricate microbial system communicates with via vagus nerve, immune system, enteric nervous enteroendocrine production metabolites, such as short-chain fatty acids. Preclinical data has demonstrated that MGB influences neurotransmission, neurogenesis, myelination, dendrite formation blood barrier development, modulates function behaviour patterns, as, social interaction, stress management locomotor activity. Furthermore, preliminary clinical studies suggest altered gut microbiota profiles in schizophrenia. Unravelling context an evolving dimensional framework schizophrenia may provide more complete understanding neurobiological architecture this condition offers possibility translational interventions.

Language: Английский

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Epigenetic Regulation of the Social Brain

Trends in Neurosciences, Journal Year: 2019, Volume and Issue: 42(7), P. 471 - 484

Published: May 15, 2019

Language: Английский

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