Profiling of extracellular vesicle‐bound miRNA to identify candidate biomarkers of chronic alcohol drinking in non‐human primates

2021 ◽  
Author(s):  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Suhas Sureshchandra ◽  
Tianyu Pan ◽  
Steven W. Gonzales ◽  
...  
Keyword(s):  
Alcohol Drinking ◽  
Extracellular Vesicle ◽  
Chronic Alcohol

scholarly journals Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility

2021 ◽  
Author(s):  
Tengfei Ma ◽  
Zhenbo Huang ◽  
Xueyi Xie ◽  
Xiaowen Zhuang ◽  
Matthew Childs ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Cognitive Flexibility ◽  
Alcohol Drinking ◽  
Long Term Potentiation ◽  
D1 Receptor ◽  
Chronic Alcohol ◽  
Glutamatergic Transmission ◽  
Chronic Alcohol Consumption ◽  
Cholinergic Interneurons

Exposure to addictive substances impairs flexible decision-making. Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs). However, how chronic alcohol drinking alters cognitive flexibility through CINs remains unclear. Here, we report that chronic alcohol consumption and withdrawal impaired reversal of instrumental learning. Chronic alcohol consumption and withdrawal also caused a long-lasting (21 d) reduction of excitatory thalamic inputs onto CINs and reduced pause response of CINs in the dorsomedial striatum (DMS). CINs are known to inhibit glutamatergic transmission in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) but facilitate this transmission in D2-MSNs, which may contribute to flexible behavior. We discovered that chronic alcohol drinking impaired CIN-mediated inhibition in D1-MSNs and facilitation in D2-MSNs. Importantly, in vivo optogenetic induction of long-term potentiation of thalamostriatal transmission in DMS CINs rescued alcohol-induced reversal learning deficits. These results demonstrate that chronic alcohol drinking reduces thalamic excitation of DMS CINs, compromising their regulation of glutamatergic transmission in MSNs, which may contribute to alcohol-induced impairment of cognitive flexibility. These findings provide a neural mechanism underlying inflexible drinking in alcohol use disorder.

scholarly journals Chronic Alcohol Drinking Slows Brain Development in Adolescent and Young Adult Nonhuman Primates

eNeuro ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. ENEURO.0044-19.2019 ◽  
Author(s):  
Tatiana A. Shnitko ◽  
Zheng Liu ◽  
Xiaojie Wang ◽  
Kathleen A. Grant ◽  
Christopher D. Kroenke
Keyword(s):  
Young Adult ◽  
Brain Development ◽  
Alcohol Drinking ◽  
Nonhuman Primates ◽  
Adolescent And Young Adult ◽  
Chronic Alcohol

Long-term changes of salivary exoglycosidases and their applicability as chronic alcohol-drinking and dependence markers

2017 ◽  
Vol 20 (1) ◽  
pp. 64-75 ◽  
Author(s):  
Napoleon Waszkiewicz ◽  
Ewa Maria Kratz ◽  
Sylwia Chojnowska ◽  
Anna Zalewska ◽  
Krzysztof Zwierz ◽  
...  
Keyword(s):  
Alcohol Drinking ◽  
Chronic Alcohol ◽  
Long Term Changes

scholarly journals Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Yang Chen ◽  
Hu Chen ◽  
Kana Hamada ◽  
Eleonora Gatta ◽  
Ying Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alcohol Drinking ◽  
Alcohol Withdrawal ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Alcohol Exposure ◽  
Immune Gene ◽  
Chronic Alcohol ◽  
Chronic Alcohol Exposure

AbstractAlcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.

scholarly journals Tu1819 Chronic Alcohol Drinking Exacerbates Liver Injury in High Fructose Diet Fed Mice

2012 ◽  
Vol 142 (5) ◽  
pp. S-1025
Author(s):  
Ming Song ◽  
Theresa S. Chen ◽  
Craig J. McClain
Keyword(s):  
Liver Injury ◽  
Alcohol Drinking ◽  
Chronic Alcohol ◽  
High Fructose Diet ◽  
High Fructose
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