Nrf2 regulates the arginase 1⁺ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice.

ABSTRACT: The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1⁺ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1⁺ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TRE

SUBMITTER: He L 

PROVIDER: S-EPMC9622811 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature