KCa2 channel positive modulation reduces alcohol drinking in female C57BL/6J mice

Alcohol, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Sex-dependent factors of alcohol and neuroimmune mechanisms

Neurobiology of Stress, Journal Year: 2023, Volume and Issue: 26, P. 100562 - 100562

Published: Aug. 3, 2023

Excessive alcohol use disrupts neuroimmune signaling across various cell types, including neurons, microglia, and astrocytes. The present review focuses on recent, albeit limited, evidence of sex differences in biological factors that mediate responses to underlying systems may influence drinking behaviors. Females are more vulnerable than males the neurotoxic negative consequences chronic drinking, reflected by elevations pro-inflammatory cytokines inflammatory mediators. Differences cytokine, microglial, astrocytic, genomic, transcriptomic suggest females reactive neuroinflammatory changes after exposure. growing body supports innate immune modulate synaptic transmission, providing a mechanistic framework examine sex-differences neurocircuitry. Targeting be viable strategy for treating AUD, but research is needed understand sex-specific mechanisms.

Language: Английский

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Cell-type brain-region specific changes in prefrontal cortex of a mouse model of alcohol dependence

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 190, P. 106361 - 106361

Published: Nov. 20, 2023

The prefrontal cortex is a crucial regulator of alcohol drinking, and dependence, other behavioral phenotypes associated with AUD. Comprehensive identification cell-type specific transcriptomic changes in dependence will improve our understanding mechanisms underlying the excessive use refine targets for therapeutic development. We performed single nucleus RNA sequencing (snRNA-seq) Visium spatial gene expression profiling on medial (mPFC) obtained from C57BL/6 J mice exposed to two-bottle choice-chronic intermittent ethanol (CIE) vapor exposure (2BC-CIE, defined as dependent group) paradigm which models including escalation drinking. Gene co-expression network analysis differential identified highly dysregulated networks multiple cell types. Dysregulated modules their hub genes suggest novel understudied studying molecular contributing state. A subtype inhibitory neurons was most alcohol-sensitive type contained downregulated module; this module Cpa6, previously by GWAS be consumption. an astrocytic Gpc5 significantly upregulated alcohol-dependent group. To knowledge, there are no studies linking Cpa6 phenotype. also neuroinflammation related types, specifically enriched microglia, further implicating Here, we present comprehensive atlas mediated mPFC identify type-specific implicated dependence.

Language: Английский

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Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice

Neurobiology of Stress, Journal Year: 2023, Volume and Issue: 24, P. 100542 - 100542

Published: April 28, 2023

Hyperkateifia and stress-induced alcohol cravings drive relapse in individuals with use disorder (AUD). The brain stress signal norepinephrine (also known as noradrenaline) tightly controls cognitive affective behavior was thought to be broadly dysregulated AUD. locus coeruleus (LC) is a major source of forebrain norepinephrine, it recently discovered that the LC sends distinct projections addiction-associated regions suggesting alcohol-induced noradrenergic changes may more region-specific than originally thought. Here we investigated whether ethanol dependence alters adrenergic receptor gene expression medial prefrontal cortex (mPFC) central amgydala (CeA), these mediate impairment negative state withdrawal. We exposed male C57BL/6J mice chronic intermittent vapor-2 bottle choice paradigm (CIE-2BC) induce dependence, assessed reference memory, anxiety-like transcript levels during 3-6 days Dependence bidirectionally altered mouse α1 β mRNA levels, potentially leading reduced mPFC signaling enhanced influence over CeA. These were accompanied by long-term retention deficits shift search strategy modified Barnes maze task, well greater spontaneous digging hyponeophagia. Current clinical studies are evaluating compounds treatment for AUD-associated hyperkatefia, our findings can contribute refinement therapies increasing understanding specific neural systems symptoms targeted.

Language: Английский

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A Standardized Extract of Zingiber officinale Roscoe Regulates Clinical and Biological Outcomes in Two Different EAE Mouse Models

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 278 - 278

Published: Jan. 23, 2025

Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and neuronal damage. Current MS therapies are unsatisfactory, new encouraged. A correlation between nutritional intake has been speculated. Supplementation approved immunomodulatory therapy with herbal medicines possessing antioxidant anti-inflammatory activities could provide benefits to patients. Ginger one most widely consumed dietary supplements in world, commonly used traditional medicine. Studies demonstrated that ginger may also be beneficial management neurodegenerative diseases. The aim this study investigate therapeutic potential ginger. Methods: standardized Zingiber officinale Roscoe extract (ZOE) was orally administered for 14 days. Two experimental autoimmune encephalomyelitis (EAE) models mice were used. PLP139-151-EAE relapsing-remitting model MOG35–55-EAE model. Clinical score, von Frey, hot plate, rotarod tests behavioral tests. ELISA Western blotting measure cytokines levels. Evans Blue content determined spectrophotometrically. Results: ZOE attenuated motor disability pain hypersensitivity both had no effect on body weight loss. reduced blood–brain barrier (BBB) permeability PLP-EAE levels circulating (Il-6, IL-17) MOG-EAE spinal overexpression models. Conclusions: improves EAE symptoms attenuates proinflammatory response models, representing promising nutraceutical support conventional approach MS.

Language: Английский

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Alcohol Consumption Modulates the Development of Chronic Pain in COVID-19 Patients: A Network Meta-Analysis

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(2), P. 409 - 422

Published: Feb. 4, 2025

The mechanisms underlying the onset and progression of chronic pain in COVID-19 patients have been understudied. Using network meta-analysis, we previously demonstrated that alcohol augments symptoms pathologies possibly by inducing a severe cytokine storm. We others also reported acute consumption produces analgesic effects, while results hyperalgesia pain. This study aimed to identify influence on publicly available curated gene expression data sets differentially expressed genes (DEGs) prefrontal cortex (PFC) amygdala patients, employed bioinformatics application, QIAGEN ingenuity pathway analysis (IPA), key signaling pathways, upstream regulators, biological functions these brain areas known play role Canonical revealed activation neuropathic pathways involving storm, S100 family, IL-6, neuroinflammation. IPA's builder was construct map shared molecules between pain-related constructs (discomfort, pain, inflammatory pain). simulation inhibited this map. To COVID-19, overlaid DEGs from PFC onto networks, mimicking during SARS-CoV-2 infection. Upregulation predicted an increase as well PFC. Our suggest directly inhibits presence exaggerates impaired signaling, neuroinflammation, CNS providing novel insights into associated with patients.

Language: Английский

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Chronic intermittent ethanol produces nociception through endocannabinoid-independent mechanisms in mice

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110502 - 110502

Published: May 1, 2025

Language: Английский

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Increased Incidence of Depression and Chronic Pain in Traumatic Spinal Cord Injury Patients With Pre-Injury Alcohol Use Disorder: Longitudinal Analysis of Insurance Claim Database

Neurotrauma Reports, Journal Year: 2024, Volume and Issue: 5(1), P. 28 - 36

Published: Jan. 1, 2024

Alcohol use disorder (AUD) increases risk of traumatic spinal cord injury (SCI) and is associated with depression, anxiety, chronic pain. Given that these neuropsychiatric morbidities are frequently observed in SCI patients, the effects pre-injury AUD on or pain were analyzed using an insurance claim database. Of 10,591 507 had AUD-associated claims a 12-month period before injury. Those AUD-positive patients showed distinct demographic characteristics, including greater representation men, younger age, more comorbidities, lower coverage by commercial insurance, cervical-level injuries. The group also elevated comorbidity However, multi-regression analysis revealed increased odds ratio (OR) de novo diagnosis post-SCI depression 6 months (1.671; 95% confidence interval [CI]: 1.124, 2.483) 1 year post-injury (1.511; CI: 1.071, 2.131). OR anxiety was unaffected AUD. Finally, after SCI, (1.545; 1.223, 1.951). Thus, may be factor for development SCI.

Language: Английский

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Excessive alcohol intake produces persistent mechanical allodynia and dysregulates the endocannabinoid system in the lumbar dorsal root ganglia of genetically-selected Marchigian Sardinian alcohol-preferring rats

Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107462 - 107462

Published: Oct. 11, 2024

Epidemiological data indicate a strong association between alcohol use disorder (AUD) and neuropathic pain. Genetically-selected Marchigian Sardinian alcohol-preferring (msP) rats exhibit high preference for compared with their background strain (Wistar rats), but sensitivity to mechanical allodynia after chronic exposure is unknown. The present study the development of "low, non-pathological drinker" Wistar "high msP using two-bottle choice (2BC) free-access procedure. Several studies reported involvement endocannabinoids (eCBs) in modulating allodynia, there are no on role alcohol-related allodynia. Thus, assessed eCBs related lipid species lumbar dorsal root ganglia (DRG) correlated them our model. We found that male female developed persistent during protracted abstinence from alcohol, presenting sign recovery, as opposed rats. This effect directly total intake. Notably, we correlation lower DRG 2-arachidonoylglycerol (2-AG) levels higher both sexes not Moreover, alcohol-exposed abstinent females males exhibited significant alterations thromboxane B2 prostaglandin E2/prostaglandin D2 naive These findings demonstrate 2-AG metabolism altered prolonged represents potentially interesting pharmacological target treatment abstinence.

Language: Английский

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Long‐lasting mechanical hypersensitivity and CRF receptor type‐1 neuron activation in the BNST following adolescent ethanol exposure

Alcohol Clinical and Experimental Research, Journal Year: 2023, Volume and Issue: 48(1), P. 48 - 57

Published: Nov. 14, 2023

Adolescent alcohol use can produce long-lasting alterations in brain function, potentially leading to adverse health outcomes adulthood. Emerging evidence suggests that chronic increase pain sensitivity or exacerbate existing conditions, but the potential neural mechanisms underlying these effects require further investigation. Here, we evaluate impact of ethanol vapor on mechanical over course acute and protracted withdrawal adolescent adult male female mice, its association with corticotropin-releasing factor (CRF) signaling within bed nucleus stria terminalis (BNST).

Language: Английский

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