| Research Abstract |
In an attempt to explore the molecular basis of nerve regeneration process, we have employed differential display-PCR to identify genes whose mRNA expression were up-regulated in injured hypoglossal motor neurons, and succeeded in isolating both novel as well as known molecules with possible association with neuronal survival and regeneration. To rescue or repair injured neurons, the adenovirus mediated gene transfer is one of intriguing means. We thus attempted to establish adenovirus mediated gene transfer system using rat. After establishing the gene transfer system specific to injured motor neurons, we have revealed distinct functional differences between two signaling pathways (P13K-mediated and ERK-mediated pathways downstream growth factor receptors) using our adenovirus system. In addition, we have also revealed a novel activity of Akt on neurite elongation both in vitro and in vivo. Functional significance of other molecules are also revealed by using this adenovirus mediated gene transfer system. For instance a novel Rho family protein TC10 was proved to have a function on neurite elongation. The results obtained in the present project provide useful tool for the nerve regeneration studies, in which the function of a certain molecule are examined in experimental animal, and also open up a possibility of therapeutic intervention in clinical conditions like brain trauma, ischaemia, or neurodegenerative conditions like ALS, Parkinson's disease, etc.
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