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 Purk...

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Autores principales:	Larisa Kavetsky, Kayla K. Green, Bridget R. Boyle, Fawad A. K. Yousufzai, Zachary M. Padron, Sierra E. Melli, Victoria L. Kuhnel, Harriet M. Jackson, Rosa E. Blanco, Gareth R. Howell, Ileana Soto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a3142fa18544a06af143d5a90ca39f0
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spelling	oai:doaj.org-article:0a3142fa18544a06af143d5a90ca39f02021-12-02T15:07:53ZIncreased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C10.1038/s41598-019-51246-12045-2322https://doaj.org/article/0a3142fa18544a06af143d5a90ca39f02019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51246-1https://doaj.org/toc/2045-2322Abstract 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 loss of PCs is detected. During the progression of PCs degeneration in Npc1 nmf164 mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding Npc1 nmf164 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.Larisa KavetskyKayla K. GreenBridget R. BoyleFawad A. K. YousufzaiZachary M. PadronSierra E. MelliVictoria L. KuhnelHarriet M. JacksonRosa E. BlancoGareth R. HowellIleana SotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-15 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Larisa Kavetsky Kayla K. Green Bridget R. Boyle Fawad A. K. Yousufzai Zachary M. Padron Sierra E. Melli Victoria L. Kuhnel Harriet M. Jackson Rosa E. Blanco Gareth R. Howell Ileana Soto Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
description	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 loss of PCs is detected. During the progression of PCs degeneration in Npc1 nmf164 mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding Npc1 nmf164 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.
format	article
author	Larisa Kavetsky Kayla K. Green Bridget R. Boyle Fawad A. K. Yousufzai Zachary M. Padron Sierra E. Melli Victoria L. Kuhnel Harriet M. Jackson Rosa E. Blanco Gareth R. Howell Ileana Soto
author_facet	Larisa Kavetsky Kayla K. Green Bridget R. Boyle Fawad A. K. Yousufzai Zachary M. Padron Sierra E. Melli Victoria L. Kuhnel Harriet M. Jackson Rosa E. Blanco Gareth R. Howell Ileana Soto
author_sort	Larisa Kavetsky
title	Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
title_short	Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
title_full	Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
title_fullStr	Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
title_full_unstemmed	Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C
title_sort	increased interactions and engulfment of dendrites by microglia precede purkinje cell degeneration in a mouse model of niemann pick type-c
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/0a3142fa18544a06af143d5a90ca39f0
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Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C

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