Natalia Quijano-Cardé

University of Pennsylvania

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Mariella De Biasi

University of Pennsylvania

Erica M. Periandri

Washington University in St. Louis

Connor Hogan

University of Pennsylvania

Kechun Yang

University of Pennsylvania

Shelley L. Berger

University of Pennsylvania

Ian McLaughlin

University of Pennsylvania

Vanessa Fleites

University of Pennsylvania

John A. Dani

University of Pennsylvania

Erika E. Perez

University of Pennsylvania

Jessica K. Shaw

University of Pennsylvania

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University of Pennsylvania

California University of Pennsylvania

Philadelphia University

Washington University in St. Louis

Baylor College of Medicine

Abramson Cancer Center

Translational Therapeutics (United States)

Southern Illinois University Edwardsville

University of Iowa

Centro di Riferimento Oncologico

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Decreased voluntary alcohol intake and ventral striatal epigenetic and transcriptional remodeling in male Acss2 KO mice

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Gábor Egervári Greg Donahue Natalia Quijano-Cardé Connor Hogan Erica M. Periandri

ABSTRACT Metabolic-epigenetic interactions are emerging as key pathways in regulating alcohol-related transcriptional changes in the brain. We previously demonstrated that this is mediated by the metabolic enzyme Acetyl-CoA synthetase 2 (Acss2), which is nuclear and chromatin-bound in neurons. Mice lacking Acss2 fail to deposit alcohol-derived acetate onto histones in the brain and show no conditioned place preference for ethanol reward. Here, we explored the role of this pathway during voluntary alcohol intake. We found that Acss2 KO mice consumed significantly less alcohol during drinking-in-the-dark, and this effect was primarily driven by males. We performed genome-wide transcriptional profiling of 7 key brain regions implicated in alcohol and drug use, and found that, following drinking, Acss2 KO mice exhibited blunted gene expression in the ventral striatum, and similar to the behavioral differences, transcriptional dysregulation was more pronounced in male mice. Further, we found that the gene expression changes were associated with depletion of ventral striatal histone acetylation (H3K27ac) in Acss2 KO mice compared to WT. Taken together, our data suggest that Acss2 plays an important role in orchestrating ventral striatal epigenetic and transcriptional changes during voluntary alcohol drinking, especially in males. Consequently, targeting this pathway could be a promising new therapeutic avenue.

10.1101/2023.12.04.569964

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Citations (1)

CHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal

Neuropharmacology (2023)

Kechun Yang Ian McLaughlin Jessica K. Shaw Natalia Quijano-Cardé John A. Dani

Nicotine withdrawal

10.1016/j.neuropharm.2023.109547

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Citations (2)

Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine

Neuropsychopharmacology (2015)