The 15q11-q13 chromosomal region contains genes encoding for GABA-A receptor subunits and is a known region of epigenetic modification associated with the development of neurodevelopmental disorders. The presence of at least one additional copy of the maternal 15q11-q13 results in a syndrome (maternal dup15q) characterized by intellectual disability, autism spectrum disorder, mood disorders, and epilepsy. Catatonia is a serious syndrome of behavioral and motor dysfunction, which occurs across a variety of psychiatric, neurologic, and general medical conditions, which has successfully been treated with benzodiazepines and electroconvulsive therapy.
View Article and Find Full Text PDFPrevious 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.
View Article and Find Full Text PDF