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Our work focuses on growth factors known to play key roles in brain development and function. Some of these growth factors are found not only in the brain, but also in circulating blood platelets and we are exploring the possibility that they may be delivered to the nervous system by small vesicles derived from platelets. To this end we have generated a new mouse model allowing this hypothesis to be tested. This approach takes advantage of a major difference between mouse and primates with regard to the growth factor content of platelets. Specifically, platelets of primates contains very significant amounts of brain-deriived neurotrophic factor (BDNF), whilst BDNF is undetectable in mouse platelets. Mice were then engineered to express BDNF in megakaryocytes, with the result that their platelets contain BDNF levels comparable to humans. This work could lead to novel ways of delivering genetically encoded macromolecules to the brain over long periods of time and the potential of this approach is being explored with our colleagues at the School of Optometry. We also use extensively human neurons derived from embryonic stem cells to explore poorly understood aspects of neurotrophin signalling, including the interactions of BDNF and Neurotrophin-3 with their cognate receptors.
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Scientific Reportsno. 1 (2023): 1-7
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BRAIN COMMUNICATIONSno. 2 (2023): fcad046-fcad046
Frontiers in molecular neuroscience (2023): 1225373
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