NMDA receptor hypofunction for schizophrenia revisited: Perspectives from epigenetic mechanisms

Schizophrenia Research, Год журнала: 2019, Номер 217, С. 60 - 70

Опубликована: Апрель 9, 2019

Язык: Английский

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Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(14), С. 7671 - 7671

Опубликована: Июль 18, 2021

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, environmental influence disease, but single root cause mechanism involved yet to be conclusively determined. Consequently, identification diagnostic markers development psychotic drugs for treatment schizophrenia faces high failure rate. This article surveys etiology with particular focus on microbiota regulation microbial signaling correlates brain through vagus nerve, enteric nervous system, production postbiotics. Gut microbially produced molecules may lay groundwork further investigations into role dysbiosis pathophysiology schizophrenia. Current limited psychotherapy antipsychotic have significant side effects. Therefore, alternative therapeutic options merit exploration. The use psychobiotics alone or combination antipsychotics promote novel strategies. In view individual microbiome structure personalized response drugs, tailored targeted manipulation diversity naturally by prebiotics (non-digestible fiber) successful patients.

Язык: Английский

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Chromatin domain alterations linked to 3D genome organization in a large cohort of schizophrenia and bipolar disorder brains

Nature Neuroscience, Год журнала: 2022, Номер 25(4), С. 474 - 483

Опубликована: Март 24, 2022

Язык: Английский

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Role of histone deacetylases and their inhibitors in neurological diseases

Pharmacological Research, Год журнала: 2024, Номер unknown, С. 107410 - 107410

Опубликована: Сен. 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.

Язык: Английский

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PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia

Journal of Clinical Investigation, Год журнала: 2018, Номер 129(1), С. 364 - 372

Опубликована: Дек. 9, 2018

Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate circuitry; however, the role of HDACs in disorders, including SCZ, remains unknown humans. We previously determined HDAC2 mRNA levels were lower dorsolateral prefrontal cortex (DLPFC) tissue from donors SCZ compared controls. Here we investigated relationship between vivo HDAC expression and impairment patients matched healthy controls using [11C]Martinostat positron emission tomography (PET).In a case-control study, relative uptake was 14 or schizoaffective disorder (SCZ/SAD) 17 hypothesis-driven region-of-interest analysis unbiased whole brain voxel-wise approaches. Clinical measures, MATRICS consensus battery, administered.Relative DLPFC SCZ/SAD controls, positively correlated performance scores across groups. also showed dorsomedial orbitofrontal gyrus, higher cerebral white matter, pons, cerebellum controls.These findings provide evidence dysregulation suggest altered may impact function humans.National Institute Mental Health (NIMH), Brain Behavior Foundation, Massachusetts General Hospital (MGH), Athinoula A. Martinos Center for Biomedical Imaging, National Imaging Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program.

Язык: Английский

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Epigenetics of childhood trauma: Long term sequelae and potential for treatment

Neuroscience & Biobehavioral Reviews, Год журнала: 2021, Номер 132, С. 1049 - 1066

Опубликована: Ноя. 3, 2021

Childhood trauma (CT) can have persistent effects on the brain and is one of major risk factors for neuropsychiatric diseases in adulthood. Recent advances field epigenetics suggest that epigenetic such as DNA methylation histone modifications, well regulatory processes involving non-coding RNA are associated with long-term sequelae CT. This narrative review summarizes current knowledge basis CT describes studies animal models human subjects examining how epigenome transcriptome modified by brain. It discusses psychological pharmacological interventions counteract changes induced need to establish longitudinal assessment after developing more effective diagnostics treatment strategies based targets.

Язык: Английский

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The Effect of Probiotic Supplementation on the Gut–Brain Axis in Psychiatric Patients

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(5), С. 4080 - 4099

Опубликована: Май 6, 2023

The pathophysiology of several psychiatric diseases may entail disturbances in the hypothalamic–pituitary–adrenal (HPA) axis and metabolic pathways. Variations how these effects present themselves be connected to individual variances clinical symptoms treatment responses, such as observation that a significant fraction participants do not respond current antipsychotic drugs. A bidirectional signaling pathway between central nervous system gastrointestinal tract is known microbiota–gut–brain axis. large small intestines contain more than 100 trillion microbial cells, contributing intestinal ecosystem’s incredible complexity. Interactions microbiota epithelium can alter brain physiology affect mood behavior. There has recently been focus on relationships impact mental health. According evidence, play role neurological illnesses. Intestinal metabolites origin, short-chain fatty acids, tryptophan metabolites, bacterial components might stimulate host’s immune system, are mentioned this review. We aim shed some growing gut inducing/manipulating disorders, which pave way for novel microbiota-based therapies.

Язык: Английский

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Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms

Biomedicines, Год журнала: 2024, Номер 12(9), С. 1978 - 1978

Опубликована: Сен. 2, 2024

Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes brain structure function, impacting areas involved emotion regulation, cognition, response. Consequently, individuals exposed to high levels of ELS are at an increased risk for health disorders like depression, anxiety, post-traumatic disorders, well issues, including metabolic cardiovascular disease, cancer. This review explores the biological psychological consequences early-life adversity paradigms rodents, maternal separation deprivation limited bedding nesting. The study these experimental models have revealed that organism’s response is complex, involving genetic epigenetic mechanisms, associated with dysregulation physiological systems nervous, neuroendocrine, immune systems, a sex-dependent fashion. Understanding impact crucial developing effective interventions preventive strategies humans stressful traumatic childhood.

Язык: Английский

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Epigenomics of Major Depressive Disorders and Schizophrenia: Early Life Decides

International Journal of Molecular Sciences, Год журнала: 2017, Номер 18(8), С. 1711 - 1711

Опубликована: Авг. 4, 2017

Brain development is guided by the interactions between genetic blueprint and environment. Epigenetic mechanisms, especially DNA methylation, can mediate these may also trigger long-lasting adaptations in developmental programs that increase risk of major depressive disorders (MDD) schizophrenia (SCZ). Early life adversity a factor for MDD/SCZ persistent genome-wide changes methylation at genes important to early, but mature, brain function, including neural proliferation, differentiation, synaptic plasticity, among others. Moreover, variations controlling dynamic early are thought influence later epigenomic SCZ. This finding corroborates high load neurodevelopmental origin SCZ shows epigenetic responses environment are, least part, genetically controlled. Interestingly, variants influencing enriched from association studies (GWAS) on supporting role neurodevelopment. Overall, appear be controlled different degrees genetics MDD/SCZ, even though potential reversibility processes offer new hope timely therapeutic interventions MDD/SCZ.

Язык: Английский

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Neurobiological effects of aerobic exercise, with a focus on patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience, Год журнала: 2019, Номер 269(5), С. 499 - 515

Опубликована: Май 21, 2019

Язык: Английский

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