The influence of neurotrophin signalling upon the generation of myelin
The neurotrophins are a family of growth factors essential for normal nervous system development and function. Our laboratory is interested in the structure, biochemistry, and mechanisms of neurotrophin signaling, as well as several aspects of their biology, in particular the role they play in the myelinating process. In this regard, we are particularly interested in the impact that Brain Derived Neurotrophic Factor (BDNF) has upon the interactions between neurons and glial cells that regulate development of both central and peripheral myelin.
We have recently made important discoveries regarding the influence that BDNF exerts upon the development of peripheral nervous system myelin. Myelin in the peripheral nervous system is generated by Schwann cells, and wraps around many axons to provide electrical insulation and metabolic support to neurons. Myelin itself is an unusual substance; consisting of a mixture of proteins, which constitute 15–30% of its mass; and lipids, which constitute the remaining 70–85%. Cholesterol is an essential constituent of myelin, but the primary lipid of myelin is a glycolipid called galactocerebroside. We have made interesting discoveries that suggest that BDNF can regulate cholesterol synthesis in Schwann cells. To determine the precise influence that BDNF exerts upon the generation of myelin lipids, we have generated transgenic mice that have BDNF receptors genetically deleted in Schwann cells. This project will investigate the lipid profile of myelin, its development, how it changes with ageing, and whether these transgenic mice exhibit alterations to the normal lipid content of myelin.
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