RMS-BDNFCNSREPAIR · Back to basics: reactivating fundamental processes that repair the developing brain to rebuild neuronal circuits following injury
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-08-11 → 2009-08-10
- EU contribution
- €216,291
- Participants
- 1
- Scheme
- IIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - RMS-BDNFCNSRepair (Back to basics ? reactivating fundamental processes that repair the developing brain to rebuild neuronal circuits following injury.)
The overall objective of the proposal was to increase our understanding on how to reproduce within the mature brain the natural repair that follows injury to the immature nervous system, therefore improving recovery from brain injury. The project used our well-established model of nervous system injury, namely the rat olivocerebellar path, to investigate the mechanisms by which one growth factor, called BDNF, recreated spontaneous developmental olivary climbing fibre axon reinnervation onto mature cerebellar Purkinje cells. During the project we identified three factors that regulated gene expression, i.e. transcription factors, and two groups of molecules that controlled cell to cell interactions, i.e. extracellular matrix molecules, whose expression changed during both spontaneous and BDNF-induced olivocerebellar reinnervation. In order to facilitate this investigation we optimised a simpler model of olivocerebellar reinnervation, grown in culture. The importance of this technical advancement was that it allowed us to separately examine the relative contribution of the newly growing connections versus the target Purkinje cells on the success or failure of neural circuit repair. We also began testing the role of the two groups of extracellular molecules in BDNF-induced olivocerebellar reinnervation. Even though we examined one in the host laboratory, in order to study the second, which was a group of growth-inhibitory molecules called ephrins, we used transgenic mice which did not express these molecules. In addition to providing a means of testing the role of these molecules in post-injury repair, obtaining these mice established a beneficial ongoing international collaboration and increased awareness of European research in Australia.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- UNIVERSITE PIERRE ET MARIE CURIE - PARIS VI · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union