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Oligodendrogenesis increases in hippocampal grey and white matter prior to locomotor or memory impairment in an adult mouse model of tauopathy


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Ferreira, SCA ORCID: 0000-0002-0401-0615, Pitman, KA ORCID: 0000-0003-3198-9336, Summers, BS, Wang, S, Young, KM ORCID: 0000-0002-1686-3463 and Cullen, CL ORCID: 0000-0001-6929-6258 2020 , 'Oligodendrogenesis increases in hippocampal grey and white matter prior to locomotor or memory impairment in an adult mouse model of tauopathy' , European Journal of Neuroscience , pp. 1-23 , doi: 10.1111/ejn.14726.

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Myelin and axon losses are associated with cognitive decline in healthy ageing but are worse in people diagnosed with tauopathy. To determine whether tauopathy is also associated with enhanced myelin plasticity, we evaluated the behaviour of OPCs in mice that expressed a human pathological variant of microtubule-associated protein tau (MAPTP301S). By 6 months of age (P180), MAPTP301S mice overexpressed hyperphosphorylated tau and had developed reactive gliosis in the hippocampus but had not developed overt locomotor or memory impairment. By performing cre-lox lineage tracing of adult OPCs, we determined that the number of newborn oligodendrocytes added to the hippocampus, entorhinal cortex and fimbria was equivalent in control and MAPTP301S mice prior to P150. However, between P150 and P180, significantly more new oligodendrocytes were added to these regions in the MAPTP301S mouse brain. This large increase in new oligodendrocyte number was not the result of increased OPC proliferation, nor did it alter oligodendrocyte density in the hippocampus, entorhinal cortex or fimbria, which was equivalent in P180 wild-type and MAPTP301S mice. Furthermore, the proportion of hippocampal and fimbria axons with myelin was unaffected by tauopathy. However, the proportion of myelinated axons that were ensheathed by immature myelin internodes was significantly increased in the hippocampus and fimbria of P180 MAPTP301S mice, when compared with their wild-type littermates. These data suggest that MAPTP301S transgenic mice experience significant oligodendrocyte turnover, with newborn oligodendrocytes compensating for myelin loss early in the development of tauopathy.

Item Type: Article
Authors/Creators:Ferreira, SCA and Pitman, KA and Summers, BS and Wang, S and Young, KM and Cullen, CL
Keywords: NG2-glia, myelin, oligodendrocyte, fronto-temporal dementia, tau, Alzheimer's disease, microtubule-associated protein tau, oligodendrocyte progenitor cells, tauopathy
Journal or Publication Title: European Journal of Neuroscience
Publisher: Blackwell Publishing Ltd
ISSN: 0953-816X
DOI / ID Number: 10.1111/ejn.14726
Copyright Information:

Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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