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743.10 / P4 - Oligodendrocyte and myelin alterations in Alzheimer’s disease

Citation

Dwyer, S and Leung, JYK and Kirkcaldie, M and Vickers, JC and King, AE, 743.10 / P4 - Oligodendrocyte and myelin alterations in Alzheimer's disease, Neuroscience 2018, 3-7 November, San Diego, CA (2018) [Conference Extract]


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Abstract

Previous and current Alzheimer’s disease research has a strong focus on the role of neurons and amyloid-beta peptides in the progression of Alzheimer’s disease. Recent research has implicated a role for oligodendrocytes in the progression of the disease, demonstrated by focal demyelination at plaque sites and alterations to oligodendrocyte populations in animal models of early Alzheimer’s disease. The main aim of this study is to understand the effect of amyloid-beta on oligodendrocyte development or health, which may have downstream effects on myelin and contribute to the degeneration of neurons. To help us understand this, we have examined the effect of extracellular amyloid-beta on oligodendrocyte development in-vitro. Pure oligodendrocyte precursor cell (OPC) cultures were derived from mixed glial cultures from Sprague Dawley neonatal rats at postnatal day 1-3. OPCs were induced to mature into myelin-forming oligodendrocytes over 5 days in-vitro in the presence or absence of amyloid-beta. Tracing of oligodendrocyte morphology demonstrated significantly reduced branching, suggesting that oligodendrocytes exposed to 5uM amyloid-beta 1-40 and 1-42 are less mature when compared to controls. However, immunocytochemical and trace analysis demonstrated that 1uM amyloid-beta 1-40 as there was a statistically significant increase in the number of MBP-positive oligodendrocytes and branches (n=3 separate cultures per treatment, p<0.05). This suggests that low concentrations of amyloid-beta in-vitro plays a role in inducing OPC differentiation indicated by an increased number of mature oligodendrocytes. To complement in-vitro findings, we are currently investigating the effect of amyloid-beta on myelination during a learning task as well as the effect on OPC maturation in an animal model of Alzheimer’s disease. By studying a model of induced myelination, we hope to correlate the amyloid-beta present in these animals and observe differences in their myelination profiles and oligodendrocyte populations to further support our hypothesis that oligodendrocytes have a key role in Alzheimer’s disease progression.

Item Details

Item Type:Conference Extract
Keywords:Alzheimer’s disease, myloid-beta, oligodendrocyte
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Health related to ageing
UTAS Author:Dwyer, S (Mr Samuel Dwyer)
UTAS Author:Leung, JYK (Dr Jacqueline Leung)
UTAS Author:Kirkcaldie, M (Dr Matthew Kirkcaldie)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:King, AE (Professor Anna King)
ID Code:144272
Year Published:2018
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2021-05-06
Last Modified:2021-05-06
Downloads:0

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