Role of mTORC1 signaling in postnatal microglia activation preceding neurodegeneration in a mouse model for Niemann-Pick disease Type C.

ABSTRACT: In Npc1 deficient mice, postnatal developmental alterations in cerebellar microglia and Purkinje cells (PCs) are followed by early-onset neurodegeneration. Even in the absence of PC loss, microglia in Npc1nmf164 mice display hallmark features of activation during early postnatal development, including increased proliferation, enhanced phagocytic activity, and morphological changes indicative of an activated state. In this study, we investigated whether mammalian target of rapamycin complex 1 (mTORC1) drives postnatal activation of cerebellar microglia in Npc1nmf164 mice. We found that elevated CLEC7A (Dectin-1) expression and phosphorylation of S6 ribosomal protein (pS6R), a downstream target of mTORC1, co-occurred in microglial precursors within the developing white matter region (dWMR) o

SUBMITTER: Murray CE 

PROVIDER: S-EPMC12412993 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature