The Developmental Differences of Damage in Rat Brain by Systemic Kainic Acid Injection

Kim, Chang Mi; Em, Chang Sup; Jeon, Yong Hyuck; Son, Yong Ho; Kim, Hyun

Abstract

Kainic acid[KA], a glutamic acid analogue, has been widely used as a excitotoxin in the study of neurotoxicity due to its ability to induce strong excitation and to increase intracellular calcium concentration of the mature central nervous system[CNS] neurons. However, it is not well known whether KA is also strongly cytotoxic to the neurons of the postnatal brain. We have injected KA into rats at different developmental stages and have investigated the changes in the expression of c-fos[transcriptional factor and a marker of neuronal activity], heat shock proetin 72[hsp 72, a neuronal injury marker], and glial fibrillary acidic protein[GFAP, a neuronal injury marker] mRNAs, which are known to be increased in KA-induced neurotoxicity, and glyceraldehyde 3-phosphate dehydrogenase [GAPDH, a house keeping gene] mRNAs with in situ hybridization histochemistry using specific riboprobes. The expression of c-fos mRNA was first identified in the CA3 area of hippocampus from 6hr after KA treatment in P7 rats. The c-fos mRNA-expressing area and the level of expression was gradually increased from P7 to adult. Hsp 72 mRNA was first expressed in the dentate gyrus and hippocampus from 6hr after KA treatment in P2l rats. In the adult rats, hsp 72 mRNA was broadly expressed in the brain at 2hr after KA treatment. The increase of GFAP mRNA expression was first identified in Pl4 rat brain from 6hrs after KA treatment, and by the development of brain it tends to appear earlier. The expression of GAPDH mRNA, however, did not show changes after KA treatment except for the adult rats showing a slight decrease at 12hr after KA treatment. These results suggest that KA may offer different level of cytotoxicity to the developing neurons by their developmental status and the difference may be correlated with the completion of synaptogenesis and increase of KA receptor.