Back to basics: reactivating fundamental processes.. (RMS-BDNFCNSREPAIR)
Back to basics: reactivating fundamental processes that repair the developing brain to rebuild neuronal circuits following injury
Start date: Aug 11, 2007,
End date: Aug 10, 2009
The objectives of the proposal are- to improve recovery from brain injury by increasing our understanding of how to reproduce in the mature brain the natural repair that follows injury to the immature nervous system; and- to expand the applicant's battery of techniques for investigating this important international problem.We will achieve this with a multidisciplinary approach to a simple in vivo model with well-defined structure, function and repair during development, to identify mechanisms underlying repair at molecular, cellular and circuit levels.The model is the rat climbing fibre input to the cerebellum. If this path is destroyed unilaterally early in development, new connections arising from surviving neurons provide circuit repair at anatomic, synaptic and behaviour levels.Exogenous growth-factors partly recreate this plasticity in the mature cerebellum. This project will investigate the mechanisms by which, one growth factor (BDNF) recreates developmental plasticity.The investigation will involve:- surgical removal of climbing fibres from a hemicerebellum and BDNF treatment to induce plasticity.- gene array and in situ hybridisation on tissue collected during reinnervation to identify candidate genes whose expression is altered in reinnervating and target cells.- single cell RT-PCR to compare gene expression associated with reinnervation (from b) in reinnervated vs. non-reinnervated targets, since not all available targets are reinnervated.- examination of the role of each gene in reinnervation by increasing/decreasing its function by viral vector transfection of cerebellar neurons to over-express either the active molecule or relevant blocking protein.The relevance to the Specific and Work Programs is that the exchange of ideas and expertise through research training in a prestigious French laboratory will promote a mutually beneficial ongoing collaboration and increase attractiveness of European research to Australia.
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