| Research Abstract |
This study was focused on Protective Regeneration amongst wide range of neural regeneration field. Three major topics were investigated: (1)Identification of molecules, which are associated with neuronal regeneration, (2)Identification of functional consequences of various neuronal regeneration associated molecules by using adenovirus vector, (3)A therapeutic, attempts using gene transfer technique in experimental animals. In this study we have newly identified that AIGP, ADAMTS-1,CRMP-2 and etc are associated with neuronal regeneration process. In addition, we have succeeded in establishing ATF3 as a major nerve injury associated transcription factor. ATF3 expression is observed in almost all neurons whose axons are damaged. One of the functional consequences of ATF3 expression in response to nerve injury, is that ATF3 together with cJun accelerates gene expressions such as Hsp27, which activates one of the strongest survival factor Akt. Next we have attempted to transfer genes, which are derived in this study as nerve regeneration associated genes, into injured neurons of rat. For instance over expression of CRMP in nerve-injured motor neurons was achieved by using adenovirus. This CRMP expression accelerated the speed of neurite elongation. These adenovirus mediated gene expression system in vivo may be a potent therapeutic approach for the neuron protection and nerve regeneration. In this study we have also revealed that the major transcription factor for DINE expression was STAT3 and ATF3/cJun heterodimer both in vitro and in vivo. 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, ischemia, spinal cord injury, and etc.
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