Study on the ischemia-induced neuronal injuries with special reference to alterations in the intracellular signaling cascades.

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In a series of our experiments, we have found that N-methyl-D--aspartate (NMDA) receptor coupled with intracellular calcium-signaling cascade is involved in the striatal ischemic injury and its remote effects on the target nuclei. Also, an intraventricular infusion of GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the striatal ischemic lesion. Furthermore, we have established an organotypic culture technique for the striatal tissue and then reproduced the NMDA-neurotoxicity on the striatal neurons in vitro which was not blocked by an activation of GABA_A receptor. In addition, overexpression of striatal enriched protein tyrosine phosphatase (STEP) was found to promote neuronal differentiation induced by a cAMP analogue in PC12 cells, suggesting that STEP may participate in neuronai modeling and/or plasticity. Therefore, we have a plan to elucidate whether a cell line changes its vulnerability to ischemic/anoxic insult by the STEP gene transfection.