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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<jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>nmf164<\/jats:italic><\/jats:sup>mouse cerebellum, microglia in the molecular layer (ML) are activated and contacting dendrites at early stages of NPC, when no loss of PCs is detected. During the progression of PCs degeneration in<jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>nmf164<\/jats:italic><\/jats:sup>mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding<jats:italic>Npc1<\/jats:italic><jats:sup><jats:italic>nmf164<\/jats:italic><\/jats:sup>mice a western diet (WD) increased microglia activation and corresponded with a more extensive degeneration of dendrites but not PC somata. Together our data suggest that microglia contribute to the degeneration of PCs by interacting, engulfing and phagocytosing their dendrites while the cell somata are still present.<\/jats:p>","DOI":"10.1038\/s41598-019-51246-1","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T10:04:04Z","timestamp":1570788244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C"],"prefix":"10.1038","volume":"9","author":[{"given":"Larisa","family":"Kavetsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla K.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget R.","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawad A. 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