Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.

ABSTRACT: Klotho is a life extension factor that has the ability to regulate the function of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), whose dysfunction in the nucleus accumbens (NAc) underlies critical aspects of the pathophysiology of major depression. Here, we study the functional relevance of klotho in the pathogenesis of depression. A chronic social defeat stress paradigm, in which mice are categorized as either susceptible or unsusceptible based on their performance in a social interaction test, was used in this study. We found that the expression of klotho was largely decreased in the NAc of susceptible mice compared to control or unsusceptible mice. Genetic knockdown of klotho in the NAc induced behavioral alterations relevant to depression in naive mice, while overexpressio

SUBMITTER: Wu HJ 

PROVIDER: S-EPMC9283408 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature