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Amyloidosis is associated with thicker myelin and increased oligodendrogenesis in the adult mouse brain

Citation

Ferreira, S and Pitman, KA and Wang, S and Summers, BS and Bye, N and Young, KM and Cullen, CL, Amyloidosis is associated with thicker myelin and increased oligodendrogenesis in the adult mouse brain, Journal of Neuroscience Research pp. 1-28. ISSN 0360-4012 (2020) [Refereed Article]

Copyright Statement

2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC

DOI: doi:10.1002/jnr.24672

Abstract

In Alzheimer's disease, amyloid plaque formation is associated with the focal death of oligodendrocytes and soluble amyloid β impairs the survival of oligodendrocytes in vitro. However, the response of oligodendrocyte progenitor cells (OPCs) to early amyloid pathology remains unclear. To explore this, we performed a histological, electrophysiological, and behavioral characterization of transgenic mice expressing a pathological form of human amyloid precursor protein (APP), containing three single point mutations associated with the development of familial Alzheimer's disease (PDGFB-APPSw.Ind, also known as J20 mice). PDGFB-APPSw.Ind transgenic mice had impaired survival from weaning, were hyperactive by 2 months of age, and developed amyloid plaques by 6 months of age, however, their spatial memory remained intact over this time course. Hippocampal OPC density was normal in P60-P180 PDGFB-APPSw.Ind transgenic mice and, by performing whole-cell patch-clamp electrophysiology, we found that their membrane properties, including their response to kainate (100 M), were largely normal. However, by P100, the response of hippocampal OPCs to GABA was elevated in PDGFB-APPSw.Ind transgenic mice. We also found that the nodes of Ranvier were shorter, the paranodes longer, and the myelin thicker for hippocampal axons in young adult PDGFB-APPSw.Ind transgenic mice compared with wildtype littermates. Additionally, oligodendrogenesis was normal in young adulthood, but increased in the hippocampus, entorhinal cortex, and fimbria of PDGFB-APPSw.Ind transgenic mice as pathology developed. As the new oligodendrocytes were not associated with a change in total oligodendrocyte number, these cells are likely required for cell replacement.

Item Details

Item Type:Refereed Article
Keywords:Alzheimer's disease, amyloid, dementia, myelin, oligodendrocyte
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Ferreira, S (Ms Solene Ferreira)
UTAS Author:Pitman, KA (Ms Kimberley Pitman)
UTAS Author:Wang, S (Dr Shiwei Wang)
UTAS Author:Summers, BS (Mr Ben Summers)
UTAS Author:Bye, N (Dr Nicole Bye)
UTAS Author:Young, KM (Associate Professor Kaylene Young)
UTAS Author:Cullen, CL (Dr Carlie Cullen)
ID Code:139542
Year Published:2020
Funding Support:National Health and Medical Research Council (1077792)
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-06-19
Last Modified:2020-07-16
Downloads:0

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