Abstract 1863 mTORC1 inhibition reduces microglial proliferation and enhance neuropathology in the cerebellum of NPC1 deficient mice during postnatal development

Previously, our laboratory found that developmental changes in microglia morphology, phagocytic activity, and gene expression precede cerebellar Purkinje Cell (PC) death in the Niemann-Pick Type C (NPC) disease mouse model Npc1nmf164. NPC is a lysosomal storage disease associated with early neurodegeneration and death caused by the deficiency of the NPC1 protein. Given that CLEC7A, a protein transiently expressed in microglia precursors during the early postnatal development of the mouse cerebellum, is overexpressed in the cerebellum of Npc1nmf164 mice at postnatal day 10 (P10), we aimed to determine the molecular mechanism by which NPC1 deficiency alters microglia postnatal development.