Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C.

ABSTRACT: Niemann Pick Type-C disease (NPC) is an inherited lysosomal storage disease (LSD) caused by pathogenic variants in the Npc1 or Npc2 genes that lead to the accumulation of cholesterol and lipids in lysosomes. NPC1 deficiency causes neurodegeneration, dementia and early death. Cerebellar Purkinje cells (PCs) are particularly hypersensitive to NPC1 deficiency and degenerate earlier than other neurons in the brain. Activation of microglia is an important contributor to PCs degeneration in NPC. However, the mechanisms by which activated microglia promote PCs degeneration in NPC are not completely understood. Here, we are demonstrating that in the Npc1^nmf164 mouse cerebellum, microglia in the molecular layer (ML) are activated and contacting dendrites at early stages of NPC, when no l

SUBMITTER: Kavetsky L 

PROVIDER: S-EPMC6788982 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature