TREM2 and major depressive disorder: Clinical and preclinical studies have consistently reported reduced Nrf2 expression in the mPFC of rodent models of depression and depressive patients.[10] Mechanistically, Nrf2 directly regulates the transcription of TREM2 by binding to its promoter region.[11] Collectively, the RORγt and Nrf2/TREM2 pathways have been established as key regulators of microglial activation and polarization.