Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
We recently defined that CaMKIV null mice exhibit drug-resistant depression behaviors. In CaMKIV null mouse reveals increased hippocampal adult neurogenesis which is correlated with depression. We examined whether stimulation of sigma-1 receptor (Sig-1R) improves depressive-like behaviors and hippocampal adult neurogenesis in both wild-type and CaMKIV null mice. Sig-1R is molecular chaperone regulating calcium efflux from the neuronal endoplasmic reticulum to mitochondria. Repeat treatment of dehydroepiandrosterone (DHEA), endogeneous Sig-1R legand, significantly ameliorated decreased hippocampal adult neurogenesis and depressive-like behaviors in olfactory bulbectomized mice. Next, we focus on depressive-like behaviors in CaMKIV null mice. Repeated stimulation of Sig-1R by treatment with the agonist SA4503 or the SSRI fluvoxamine for 14 days improves depressive-like behaviors and hippocampal adult neurogenesis in CaMKIV null mice. By contrast, treatment with paroxetine, which lacks affinity for Sig-1R, did not alter these behaviors and hippocampal adult neurogenesis. Taken together, Sig-1R stimulation increased hippocampal adult neurogenesis, which is closely associated with therapeutic target of drug-resistant depression.
