Early induction of mRNA for calbindin-D28k and BDNF but not NT-3 in rat hippocampus after kainic acid treatment.

The influence of kainic acid (KA), which induces acute seizures, on expression of mRNA for the calcium-binding protein, calbindin-D28k, brain-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 induction of BDNF mRNA was preceded by the induction of c-fos, mRNA (30 min after KA) and was followed by the induction of calbindin-D28k mRNA (3.5-fold 3 h after KA; a maximal response was at 3-6 h after KA). Region-specific changes, analyzed by immunocytochemistry and in situ hybridization, indicated that the most dramatic increases in calbindin protein and mRNA after KA treatment were in the dentate gyrus. Although calbindin-D28k and BDNF mRNAs were induced, a 3.4-3.8-fold decrease in NT-3 mRNA was observed by Northern analysis 3-24 h after KA treatment. Calbindin-D28k gene expression was also examined in rats with a chronic epileptic state characterized by recurrent seizures established with an episode of electrical stimulation-induced status epilepticus (SE). When these animals were examined 30 days post-SE, no changes in hippocampal calbindin-D28k mRNA were observed. Our findings suggest that the induction of calbindin-D28k mRNA (which may be interrelated to the induction of BDNF mRNA) is an early response which may not be related to enhanced neuronal activity or seizures per se, but rather to maintaining neuronal viability.