Stress-induced reduction of Na⁺/H⁺ exchanger isoform 1 promotes maladaptation of neuroplasticity and exacerbates depressive behaviors.

ABSTRACT: Major depression disorder (MDD) is a neuropsychiatric disorder characterized by abnormal neuronal activity in specific brain regions. A factor that is crucial in maintaining normal neuronal functioning is intracellular pH (pHi) homeostasis. In this study, we show that chronic stress, which induces depression-like behaviors in animal models, down-regulates the expression of the hippocampal Na⁺/H⁺ exchanger isoform 1, NHE1, a major determinant of pHi in neurons. Knockdown of NHE1 in CA1 hippocampal pyramidal neurons leads to intracellular acidification, promotes dendritic spine loss, lowers excitatory synaptic transmission, and enhances the susceptibility to stress exposure in rats. Moreover, E3 ubiquitin ligase cullin4A may promote ubiquitination and degradation of NHE

SUBMITTER: Li Y 

PROVIDER: S-EPMC9651740 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature