간질이 유발된 흰쥐 대뇌겉질에서 Nitric Oxide Synthase와 Neuropeptide Y의 발현변화

Abstract

Kainic acid (KA) is a frequently used excitotoxin in experimental epilepsy research. The excitatory effect of KA leads to generalized convulsions when KA is administered systematically at convulsant doses. Nitric oxide (NO) is a gaseous messenger that plays a role in neurotransmission. NO is formed by NO synthase (NOS) from arginine. Purification and molecular cloning led to identification of at least three NOS isoforms designated as neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). In the central nervous system, NO seems to be involved in plasticity and cytotoxicity. Therefore, the present study has investigated the congruence of mRNA induction and protein expression of nNOS, eNOS, iNOS and neuropeptide Y(NPY ) following KA-induced seizure activity. The patterns of NOS and NPY were studied by NADPH-diaphorase histochemistry, immunohistochemistry and RT-PCR in the rat brain. NADPH-d displayed a region-specific induction pattern. Regions of NADPH-d induction were the motor cortex and perirhinal cortex of KA treated group. Whereas NADPH-d neurons were not induced in auditory cortex, visual cortex, cingulate cortex, insular cortex, retrosplenial cortex and ectorhinal cortex of KA treated group. NPY neurons were not induced in all cortical areas of KA treated group. Subsequent to cortical neuronal induction, NADPH-d activity was increased in constitutive NADPH-d neurons of 1 and 3 days group of KA treatment. 1 and 3 days following KA administration, increased levels of nNOS, eNOS and iNOS mRNA were seen in the cerebral cortex. However, the level of NPY mRNA was decreased in 6 and 12 days after seizure. These findings demonstrate that mRNAs encoding for NOS isoforms are translated into the respective proteins following excitotoxic seizure.