Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance

Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer’s disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer’s disease. In addition, impaired insulin signaling in the Alzheimer’s di...

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Main Authors:	Zhu, Caihong, Schwarz, Petra, Abakumova, Irina, Aguzzi, Adriano
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677814/

id	pubmed-4677814
recordtype	oai_dc
spelling	pubmed-46778142015-12-31 Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance Zhu, Caihong Schwarz, Petra Abakumova, Irina Aguzzi, Adriano Research Article Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer’s disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer’s disease. In addition, impaired insulin signaling in the Alzheimer’s disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis. Public Library of Science 2015-12-14 /pmc/articles/PMC4677814/ /pubmed/26658276 http://dx.doi.org/10.1371/journal.pone.0144983 Text en © 2015 Zhu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhu, Caihong Schwarz, Petra Abakumova, Irina Aguzzi, Adriano
spellingShingle	Zhu, Caihong Schwarz, Petra Abakumova, Irina Aguzzi, Adriano Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
author_facet	Zhu, Caihong Schwarz, Petra Abakumova, Irina Aguzzi, Adriano
author_sort	Zhu, Caihong
title	Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
title_short	Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
title_full	Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
title_fullStr	Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
title_full_unstemmed	Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance
title_sort	unaltered prion pathogenesis in a mouse model of high-fat diet-induced insulin resistance
description	Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer’s disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer’s disease. In addition, impaired insulin signaling in the Alzheimer’s disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677814/
_version_	1613512549920145408

Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance

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