Ketamine Produces Antidepressant Effects by Inhibiting Histone Deacetylases and Upregulating Hippocampal Brain-Derived Neurotrophic Factor Levels in a Diisopropyl Fluorophosphate-Based Rat Model of Gulf War Illness.
The Journal of pharmacology and experimental therapeutics January 17, 2024 Ana Ribeiro-Davis, Dalia Y Al Saeedy, Fay M Jahr et al. 10 citations
In a rat model of Gulf War Illness (GWI), a single antidepressant dose of ketamine reversed epigenetic changes in the hippocampus. Ketamine inhibited the upregulation of histone deacetylase enzymes, restored acetylation at the Bdnf gene promoter, and increased brain-derived neurotrophic factor (BDNF) protein expression. It also increased dendritic spine density and altered spine types, shifting from S-type to T-type spines. These results suggest ketamine's antidepressant effect in GWI-related depression involves histone modifications that boost BDNF and reshape synaptic connections, supporting further clinical trials for GWI-related depression.