Defining the metabolic-epigenetic regulation of neuronal chromatin by alcohol

NIH RePORTER · NIH · R00 · $82,465 · view on reporter.nih.gov ↗

Abstract

Abstract Alcohol use disorder (AUD) represents a significant public health issue with substantial psychological and economic impacts on individuals, families, and communities. A critical gap persists in understanding the molecular underpinnings of alcohol addiction, particularly in the context of increasing youth binge drinking. Current treatments are limited, highlighting the need for research into the molecular mechanisms of AUD, including the role of epigenetic modifications following chronic alcohol exposure, such as those mediated by acetate via ACSS2 (Mews et al., 2019). This study focuses on the transport pathways of alcohol-derived acetate into the brain, investigating the role of monocarboxylate transporters (MCTs). The differential expression of MCT isoforms between neurons and astrocytes also suggests a complex, cell-type-specific role in AUD, warranting further investigation. This supplementary grant proposal aims to elucidate the role of MCT4 in facilitating the entry of alcohol-derived acetate into the brain, thus contributing to alcohol-induced epigenetic changes. This research is designed to build upon the foundational discoveries of Mews et al., exploring the regulation of brain histone acetylation by acetate derived from alcohol metabolism in the liver and its transport into hippocampal neurons and astrocytes. By exploring alcohol-derived acetate and its transport into neurons, this research will operate within the scope of the parent grant and complement its objectives while exploring distinct experimental aims. Additionally, this project will serve as a critical component of Naomi Kassahun’s training in molecular techniques and independent research towards a F31 grant application, integrating with her doctoral research objectives and enhancing her development as a future leader in addiction research. This alignment ensures a comprehensive approach to both advancing AUD research and fostering significant scientific development.

Key facts

NIH application ID
11082661
Project number
3R00AA027839-04S1
Recipient
BOSTON UNIVERSITY MEDICAL CAMPUS
Principal Investigator
Philipp Mews
Activity code
R00
Funding institute
NIH
Fiscal year
2024
Award amount
$82,465
Award type
3
Project period
2020-09-15 → 2026-08-31