EARLY INDUCTION OF MESSENGER-RNA FOR CALBINDIN-D-28K AND BDNF BUT NOTNT-3 IN RAT HIPPOCAMPUS AFTER KAINIC ACID TREATMENT

The influence of kainic acid (KA), which induces acute seizures, on ex pression of mRNA for the calcium-binding protein, calbindin-D-28k, bra in-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and early -response genes [c-fos, zif268 (NGFI-A), nur77 (NGFI-B)] was examined in rat hippocampus by Northern blot analysis. A significant increase ( 3.2-fold) in BDNF mRNA was observed 1 h after KA injection (12 mg/kg i .p.) and peak expression (9.4-fold) occurred 3 h after KA, The inducti on of BDNF mRNA was preceded by the induction of c-Sos, mRNA (30 min a fter KA) and was followed by the induction of calbindin-D-28k, mRNA (3 .5-fold 3 h after KA; a maximal response was at 3-6 h after KA). Regio n-specific changes, analyzed by immunocytochemistry and in situ hybrid ization, indicated that the most dramatic increases in calbindin prote in and mRNA after KA treatment were in the dentate gyrus, Although cal bindin-D-28k and BDNF mRNAs were induced, a 3.4-3.8-fold decrease in N T 3 mRNA was observed by Northern analysis 3-24 h after KA treatment, Calbindin-D-28k gene expression was also examined in rats with a chron ic epileptic state characterized by recurrent seizures established wit h an episode of electrical stimulation-induced status epilepticus (SE) . When these animals were examined 30 days post-SE, no changes in hipp ocampal calbindin-D-28k mRNA were observed. Our findings suggest that the induction of calbindin-D-28k mRNA (which may be interrelated to th e induction of BDNF mRNA) is an early response which may not be relate d to enhanced neuronal activity or seizures per se, but rather to main taining neuronal viability.