Using novel mouse models to determine the role of oligodendrocytes in disease
Motor neuron disease (MND) is a neurodegenerative disease characterised by the progressive loss of motor neurons. Recent research has identified that the surrounding glia play a critical role in both the onset and progression of MND.
This project has the capacity to use up to three novel mouse models of MND; each mouse model harbours a clinically common genetic mutation known to cause MND. Brains and spinal cords will be collected at various time points throughout disease and oligodendrocyte dynamics can be evaluated to determine at what time point oligodendrocyte dysfunction commences in disease.
Oligodendrocytes have two essential roles in the CNS – to myelinate neurons and to provide metabolic support to axon through this myelin sheath. Given more than 95% of a neuron is its axon, and axons require myelination for normal function, impaired oligodendrocyte function would negatively impact on myelin formation and subsequent capacity to metabolically support neurons. Indeed, recent research from our lab and others has begun to implicate oligodendrocyte dysfunction in MND pathogenesis.
This project will use a combination of biochemical approaches to assess gene and protein expression as well as advanced imaging techniques like SCoRe which isn’t available anywhere else in Australia and allows an in depth analysis of myelination. This can be coupled with electron microscopy to give a very thorough evaluation of oligodendrocyte function in MND; this will be a critically important study in the field particularly given the current interest in glial involvement in MND
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