Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders

Frontiers in Molecular Neuroscience, Journal Year: 2018, Volume and Issue: 11

Published: March 20, 2018

Postmortem studies reveal structural and molecular alterations of astrocytes oligodendrocytes in both the gray white matter (GM WM) prefrontal cortex (PFC) human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel may largely explain functional detected using neuroimaging techniques use disorders (AUDs). Moreover, due crucial roles neurotransmission signal conduction, these cells are very likely major players mechanisms underpinning alcoholism-related connectivity disturbances between PFC relevant interconnecting brain regions. The glia-mediated etiology alcohol-related damage is multifactorial since metabolic, hormonal, hepatic hemodynamic factors as well direct actions ethanol its metabolites have potential disrupt distinct aspects neurobiology. Studies animal models alcoholism postmortem brains identified astrocyte markers altered response significant exposures during withdrawal, such gap-junction proteins, glutamate transporters enzymes related gamma-aminobutyric acid (GABA) metabolism. Changes proteins their regulatory pathways would not only cause GM neuronal dysfunction, but also ability WM axons convey impulses. In addition, alters expression myelin oligodendrocyte transcription important for maintenance plasticity sheaths GM. concomitant epigenetic DNA histone modifications microRNAs (miRNAs) that profound gene protein translation. Knowledge available about interactions at Nodes Ranvier (NR), gap junction-based astrocyte-oligodendrocyte contacts other forms cell-to-cell communication now understood be critical formation myelin. Close suggest therapies based on a specific cell type pathology will require better understanding different types, considering possibility combined approaches more effective therapies.

Language: Английский

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A biological framework for emotional dysregulation in alcohol misuse: from gut to brain

Molecular Psychiatry, Journal Year: 2020, Volume and Issue: 26(4), P. 1098 - 1118

Published: Dec. 7, 2020

Language: Английский

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Epigenetics of alcohol use disorder—A review of recent advances in DNA methylation profiling

Addiction Biology, Journal Year: 2021, Volume and Issue: 26(6)

Published: Feb. 3, 2021

Alcohol use disorder (AUD) is a major contributor to morbidity and mortality worldwide. Although there heritable component, the etiology of AUD complex can involve environmental exposures like trauma be associated with many different patterns alcohol consumption. Epigenetic modifications, which mediate influence genetic variants variables on gene expression, have emerged as an important area research. Over past decade, number studies investigating DNA methylation, form epigenetic modification, has grown rapidly. Yet we are still far from understanding how methylation contributes or reflects aspects AUD. In this paper, reviewed discussed field evolved. We found that global candidate did not produce replicable results. To assess whether findings epigenome-wide association (EWAS) were replicated, aggregated significant across identified 184 genes 15 ontological pathways differentially methylated in at least two four three studies. These repeatedly enrichment immune processes, line recent developments suggesting system may altered Finally, current limitations make recommendations design future resolve outstanding questions.

Language: Английский

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Neurobiology of Addiction

Springer eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 51

Published: Jan. 1, 2023

Language: Английский

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Recommendations, guidelines, and best practice for the use of human induced pluripotent stem cells for neuropharmacological studies of neuropsychiatric disorders

Neuroscience Applied, Journal Year: 2023, Volume and Issue: 2, P. 101125 - 101125

Published: Jan. 1, 2023

The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models advanced our knowledge regarding NPDs, we still lack basic the underlying pathophysiological mechanisms. Moreover, there is an urgent need for highly effective therapeutics NPDs. Human induced pluripotent stem cells (hiPSCs) generated somatic enabled scientists to create brain a patient-specific manner. However, are challenges use hiPSCs that be addressed. In current paper, consideration best practices neuropharmacological will discussed. Specifically, provide recommendations practice patient recruitment, collecting demographic, clinical, medical (before after treatment response), diagnostic (including scales) genetic data donors. We highlight considerations donor genetics sex, addition discussing biological technical replicates. Furthermore, present views on selecting control groups/lines, experimental designs, conducting studies hiPSC-based context doing so, explore key issues field concerning reproducibility, statistical analysis, how translate vitro into clinically relevant observations. aim this article resource hiPSC researchers perform robust reproducible studies, ultimate improving identification translation novel therapeutic drugs

Language: Английский

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Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(6), P. 1210 - 1210

Published: June 6, 2017

Numerous environmental factors such as diet, alcohol use, stress, and chemicals are known to elicit epigenetic changes, leading increased rates of cancers other diseases. The incidence head neck cancer, one the most common in Taiwanese males, is increasing: oral cancer nasopharyngeal carcinoma ranked fourth tenth respectively, among top ten this group, a major cause cancer-related deaths males. Previous studies have identified smoking, betel quid chewing three causes cancers; these social habits commonly observed resulting an increasing morbidity rate population. In literature review, we discuss association between specific components quid, alcohol, tobacco, occurrence cancers, lung gastrointestinal urethral cancer. We focus on regulatory mechanisms at level their oncogenic effects. review further discusses application FDA-approved drugs therapeutic strategies against

Language: Английский

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Adolescent Alcohol Exposure-Induced Changes in Alpha-Melanocyte Stimulating Hormone and Neuropeptide Y Pathways via Histone Acetylation in the Brain During Adulthood

The International Journal of Neuropsychopharmacology, Journal Year: 2017, Volume and Issue: 20(9), P. 758 - 768

Published: May 31, 2017

Adolescent intermittent ethanol exposure causes long-lasting alterations in brain epigenetic mechanisms. Melanocortin and neuropeptide Y signaling interact are affected by the brain. Here, persistent effects of adolescent on alpha-melanocyte stimulating hormone, melanocortin 4 receptor, expression their regulation histone acetylation mechanisms were investigated adulthood. Male rats exposed to (2 g/kg, i.p.) or volume-matched saline from postnatal days 28 41 allowed grow day 92. Anxiety-like behaviors measured elevated plus-maze test. Brain regions adult used examine changes status promoters. ethanol-exposed displayed anxiety-like showed increased pro-opiomelanocortin mRNA levels hypothalamus receptor both amygdala compared with saline-exposed rats. The alpha-Melanocyte hormone protein central medial nucleus amygdala, paraventricular nucleus, arcuate Neuropeptide decreased Histone H3K9/14 was promoter but gene promoters controls. Increased activity due emotional circuitry may play a role ethanol-induced anxiety phenotypes

Language: Английский

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Regulation of GABAA Receptor Subunit Expression in Substance Use Disorders

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(12), P. 4445 - 4445

Published: June 22, 2020

The modulation of neuronal cell firing is mediated by the release neurotransmitter GABA (γ-aminobuytric acid), which binds to two major families receptors. ionotropic GABAA receptors (GABAARs) are composed five distinct subunits that vary in expression brain region and type. action on GABAARs modulated a variety clinically pharmacologically important drugs such as benzodiazepines alcohol. Exposure abuse these substances disrupts homeostasis induces plasticity GABAergic neurotransmission, often via regulation receptor expression. Here, we review GABAAR subunit adaptive pathological plasticity, with focus substance use. We examine factors influencing genes including 5′ 3′ untranslated regions, variations DNA methylation, immediate early transcription regulate expression, translational post-translational modifications, other forms beyond Advancing our understanding regulating during well use withdrawal will provide insight into role signaling disorders, contribute development novel targeted therapies.

Language: Английский

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Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight

Pharmacological Reviews, Journal Year: 2021, Volume and Issue: 73(2), P. 571 - 596

Published: Feb. 17, 2021

The gut microbiome modulates neurochemical function and behavior has been implicated in numerous central nervous system (CNS) diseases, including developmental, neurodegenerative, psychiatric disorders. Substance use disorders (SUDs) remain a serious threat to the public well-being, yet involvement drug abuse received very little attention. Studies of mechanisms underlying SUDs have naturally focused on CNS reward circuits. However, significant body research accumulated over past decade that unwittingly provided strong support for participation reward. β-Lactam antibiotics employed increase glutamate transporter expression reverse relapse-induced release glutamate. Sodium butyrate used as histone deacetylase inhibitor prevent drug-induced epigenetic alterations. High-fat diets alter because extensive overlap circuitry mediating them. This review article casts these approaches different light makes compelling case modulation SUDs. Few factors structure composition more than high-fat diet, is an endogenous product bacterial fermentation. Drugs such cocaine, alcohol, opiates, psychostimulants also modify microbiome. Therefore, their effects must be viewed complex background cotreatment-induced dysbiosis. Consideration should beneficial expanding understanding aiding design new therapies based opposing abused drugs host's commensal community.

Significance Statement

Proposed substance fail acknowledge impact antibiotics, sodium butyrate, are seeking reward, overlooking notable capacity treatments aims stimulate abuse–gut interactions by illustrating how share with fat-laden ability host microbial

Language: Английский

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Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine

Frontiers in Behavioral Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Feb. 26, 2021

Binge drinking and alcohol abuse are common during adolescence cause both cognitive deficits lasting cholinergic pathology in the adult basal forebrain. Acetylcholine is anti-inflammatory studies using preclinical adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2 day on/2 off from postnatal [P]25 to P54) model of human binge report decreased forebrain neurons (BFCNs) induction proinflammatory genes that persist long into adulthood. Recent link AIE-induced neuroimmune activation pathology, but underlying mechanisms contributing persistent loss BFCNs unknown. We treatment with cholinesterase inhibitor galantamine (4.0 mg/kg, i.p.) administered AIE (i.e., P25–P54) or following conclusion P57–P72) recovered neuron phenotype markers ChAT, TrkA, p75 NTR ) somal shrinkage residual ChAT + known AIE-exposed adults. Galantamine also AIE-increased expression receptors TLR4 RAGE, endogenous TLR4/RAGE agonist HMGB1, transcription marker pNF-κB p65. Interestingly, we find express increased p65 IR neurons, consistent intracellular HMGB1-TLR4/RAGE signaling within BFCNs. epigenetic silencing H3K9me2 H3K9me3) occupancy at gene promoters TrkA ). The finding no changes total NeuN reversal loss, TLR4/RAGE-pNF-κB signals, suggests does not cell death, rather phenotype. Together, these data suggest induces HMGB1-TLR4/RAGE-pNF-κB causing through histone result BFCN can be prevented restored by galantamine.

Language: Английский

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