Alcohol Use Disorder Associated GeneFNDC4Alters Glutamatergic and GABAergic Neurogenesis DOI Creative Commons

Xiujuan Zhu,

August John, Liping Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

Large-cohort genome-wide association studies (GWAS) for alcohol use disorder (AUD) and AUD-related phenotypes have identified more than one hundred genetic loci. Functional study of those GWAS-identified loci might represent an important step toward understanding AUD pathophysiology. We found that which are splicing quantitative trait (sQTLs) the fibronectin III domain containing 4 ( FNDC4 ) gene in brain were by GWAS both drug treatment outcomes risk. However, function how it contribute to pathophysiology remain unknown. In present study, we characterized locus-associated splice isoforms, suggested alternative results loss-of-function FNDC4. also investigated using CRISPR/cas9 editing, creation human induced pluripotent stem cell (iPSC)-derived neural organoids joined with single-nucleus RNA sequencing. observed knock-out (KO) resulted a striking shift relative proportions glutamatergic GABAergic neurons iPSC-derived organoids, suggesting possible role neurogenesis. explored potential mechanism(s) -dependent neurogenesis mediating cell-cell interaction. summary, this series experiments indicates plays regulating cerebral cortical brain. This regulation may response pharmacotherapy as well effects on

Язык: Английский

Gut Microbiome-Liver-Brain axis in Alcohol Use Disorder. The role of gut dysbiosis and stress in alcohol-related cognitive impairment progression: possible therapeutic approaches. DOI Creative Commons
Emilio Merlo Pich, Ioannis Tarnanas, Patrizia Brigidi

и другие.

Neurobiology of Stress, Год журнала: 2025, Номер 35, С. 100713 - 100713

Опубликована: Фев. 8, 2025

The Gut Microbiome-Liver-Brain Axis is a relatively novel construct with promising potential to enhance our understanding of Alcohol Use Disorder (AUD), and its therapeutic approaches. Significant alterations in the gut microbiome occur AUD even before any other systemic signs or symptoms manifest. Prolonged inappropriate alcohol consumption, by affecting microbiota mucosa permeability, thought contribute development behavioral cognitive impairments, leading Alcohol-Related Liver Disorders potentially progressing into alcoholic cirrhosis, which often associated severe impairment related neurodegeneration, such as hepatic encephalopathy dementia. critical role further supported efficacy FDA-approved treatments for cirrhosis (i.e., lactulose rifaximin). To stimulate new research, we hypothesize that interactions between maladaptive stress response constitutional predisposition neurodegeneration underlie progression conditions Clinical Concerns impairment, represent significant costly burden society. Early identification individuals at risk developing these could help prioritize integrated interventions targeting different substrates axis. Specifically, addiction medications, modulators, stress-reducing interventions, and, possibly soon, agents reduce steatosis/fibrosis will be discussed context digitally explicit goal this treatment performed on early stage disorder would transition from those Common strategy recommended most neurological neurodegenerative disorders.

Язык: Английский

Процитировано

1

Recognition, management, and patient perspectives of impulsive-compulsive disorders in Parkinson’s disease DOI Creative Commons
Mirjam Wolfschlag, Gustav Cedergren Weber, Jonathan Timpka

и другие.

Journal of Parkinson s Disease, Год журнала: 2025, Номер unknown

Опубликована: Март 16, 2025

Background Impulsive-compulsive disorders (ICDs) are commonly acknowledged as side effects of dopaminergic therapy in Parkinson’s disease (PD). While many large-scale studies have focused on prevalences and high-risk treatments, little is known about practical management ICDs clinical care patients’ experiences. Objective To investigate how recognized PD care, features patients with ICDs, impacted by their ICD. Methods Questionnaires were sent to all who reported ICD symptoms the Swedish quality register for Skåne County (n = 170) medical records screened mention ICDs. Core subjects communication between clinician patient, course impact different life domains. Results Despite sufficient awareness risk during treatment, there was limited staff regarding Only 49% had part only 14% been asked it. Additionally, collaboration psychiatry rare (12%). severity increased over time ongoing most a mild moderate close relationships, family, mental physical health. Conclusions This study identified insufficient very involvement health services. Thus, improve prevention should be recognized, monitored treated more systematically routine services increased.

Язык: Английский

Процитировано

0

Acetaldehyde-driven mRNA methylation and expression changes in ethanol-metabolizing enzyme genes DOI Creative Commons

Ji Sun Koo,

Qiansheng Zhan, Huiping Zhang

и другие.

Epigenetics, Год журнала: 2025, Номер 20(1)

Опубликована: Апрель 19, 2025

This study examines how the alcohol metabolite acetaldehyde modulates mRNA methylation and expression of ethanol-metabolizing genes, uncovering its epigenetic role in ethanol metabolism. Using neuron-like (SH-SY5Y) non-neuronal (SW620) cellular models, we examined effects chronic intermittent (CIA) exposure subsequent withdrawal (CIA+WD) on global RNA m6A modifications three brain genes: CAT (catalase), CYP2E1 (cytochrome P450 2E1), ALDH2 (aldehyde dehydrogenase 2). A 3-week CIA exposure, with or without 24-hour withdrawal, did not significantly alter levels either cell line. However, exposure/withdrawal induced hypermethylation at stop codon regions (CIA: p = 0.002; CIA+WD: 0.055) 0.077; 0.036) SH-SY5Y cells, but SW620 cells. Furthermore, was upregulated both types following (SH-SY5Y: 0.073 [CIA] 0.00002 [CIA+WD]; SW620: 0.0009 0.00008 [CIA+WD]). In contrast, remained unchanged. These findings highlight cell-specific acetaldehyde, particularly modulating ALDH2, a key enzyme

Язык: Английский

Процитировано

0

Alcohol Use Disorder Associated GeneFNDC4Alters Glutamatergic and GABAergic Neurogenesis DOI Creative Commons

Xiujuan Zhu,

August John, Liping Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 16, 2025

Large-cohort genome-wide association studies (GWAS) for alcohol use disorder (AUD) and AUD-related phenotypes have identified more than one hundred genetic loci. Functional study of those GWAS-identified loci might represent an important step toward understanding AUD pathophysiology. We found that which are splicing quantitative trait (sQTLs) the fibronectin III domain containing 4 ( FNDC4 ) gene in brain were by GWAS both drug treatment outcomes risk. However, function how it contribute to pathophysiology remain unknown. In present study, we characterized locus-associated splice isoforms, suggested alternative results loss-of-function FNDC4. also investigated using CRISPR/cas9 editing, creation human induced pluripotent stem cell (iPSC)-derived neural organoids joined with single-nucleus RNA sequencing. observed knock-out (KO) resulted a striking shift relative proportions glutamatergic GABAergic neurons iPSC-derived organoids, suggesting possible role neurogenesis. explored potential mechanism(s) -dependent neurogenesis mediating cell-cell interaction. summary, this series experiments indicates plays regulating cerebral cortical brain. This regulation may response pharmacotherapy as well effects on

Язык: Английский

Процитировано

0