BK channel deacetylation by SIRT1 in dentate gyrus regulates anxiety and response to stress.

ABSTRACT: Previous genomic studies in humans indicate that SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, is involved in anxiety and depression, but the mechanisms are unclear. We previously showed that SIRT1 is highly activated in the nuclear fraction of the dentate gyrus of the chronically stressed animals and inhibits memory formation and increases anhedonic behavior during chronic stress, but specific functional targets of cytoplasmic SIRT1 are unknown. Here, we demonstrate that SIRT1 activity rapidly modulates intrinsic and synaptic properties of the dentate gyrus granule cells and anxiety behaviors through deacetylation of BK channel α subunits in control animals. Chronic stress decreases BKα channel membrane expression, and SIRT1 activity has no rapid effects

SUBMITTER: Yu D 

PROVIDER: S-EPMC6123630 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature