Acetate enhances long-term memory in female mice by sex-, context-, and brain region–specific epigenetic and transcriptional remodeling

ABSTRACT: Metabolic control of chromatin and gene expression is emerging as a key mechanism influencing critical neuronal functions. Here, we found that the intermediary metabolite acetate enhanced long-term memory in female mice, and this was associated with epigenetic and transcriptional remodeling in the dorsal hippocampus. Acetate-enhanced memory was driven by increased acetylation of the histone variant H2A.Z and increased expression of genes implicated in spatial learning, in the female dorsal hippocampus. The effect of acetate on dorsal hippocampal histone modifications and gene expression differed markedly between the sexes during critical windows of memory consolidation and recall, and home cage exposure to acetate without the learning and memory tasks did not recapitulate these effects. These findings elucidate a role for the metabolite acetate in regulating dorsal hippocampal chromatin and gene expression, and this work outlines the ways in which acetate exposure enhances learning and memory. Here, we have deposited the raw data for the mass spectrometry experiments in this study.

INSTRUMENT(S): Orbitrap Ascend

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Gabor Egervari  

PROVIDER: MSV000095573 | MassIVE | Mon Aug 12 11:50:00 BST 2024

SECONDARY ACCESSION(S): PXD054821

REPOSITORIES: MassIVE