Role of Wnt in the decline of oligodendrocyte generation in the ageing brain

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The massive computing power of the brain depends on the insulation of nerve cell connections with myelin sheaths, by cells known as oligodendrocytes (OLs). Bundles of these 'myelinated' connections form the white matter that is very prominent in the human cortex. Although a loss of cortical white matter and myelin has been documented in cognitive decline, the causes are unknown.There is evidence that OLs are continuously lost and regenerated from a pool of OL progenitors (OPs). For unknown reasons, the ability of OPs to generate OLs declines with age, which underlies the loss of myelin and cognitive functions. The applicant has identified a key factor that drives OL generation in the adult brain and which is deregulated in ageing. This factor is known as Wnt (pronounced wint), and the aim of this project is to determine the mechanisms by which Wnt controls OP generation and OL/myelin loss in the ageing mouse brain. This will provide new knowledge on the mechanisms underlying myelin loss in ageing brain and may ultimately lead to the identification of new cellular targets for protecting myelin and preserving cognitive function.This fundamental research fits the BBSRC Research Priority of 'Healthy ageing across the lifecourse'.