ADRENALECTOMY ATTENUATES KAINIC ACID-ELICITED INCREASES OF MESSENGER-RNAS FOR NEUROTROPHINS AND THEIR RECEPTORS IN THE RAT-BRAIN

Treatment with excitotoxin kainic acid is known to increase the level of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor in the brain. In this study we have used quantitative in situ hybridization to analyse the effect of glucocorticoids on kainic acid-induced increase of nerve growth factor and brain-derived neurotrophic factor messenger RNA in the rat brain. In adrenalectomized animals, the kainic acid-mediated increase of brain-derived neurotrophic factor messenger RNA in the hippocampus and the cerebral cortex was reduced by 50% compared to sham-operated animals. The increase of nerve growth factor messenger RNA elicited by kainic acid in the dentate gyrus was almost completely abolished in adrenalectomized animals. No significant change was seen in c-fos messenger RNA in the hippocampus of adrenalectomized rat after kainic acid injection compared to sham-operated kainic acid-treated rats, while a three-fold reduction was seen in the cerebral cortex. Dexamethasone injection prior to kainic acid administration potentiated the kainic acid-induced increase of nerve growth factor messenger RNA in the dentate gyrus and the piriform cortex. In contrast, dexamethasone pretreatment did not potentiate the kainic acid-mediated increase of brain-derived neurotrophic factor messenger RNA. We also examined the effect of adrenalectomy and kainic acid injection on tropomyosin receptor kinase B and C messenger RNA, encoding essential components of high-affinity receptor for brain-derived neurotrophic factor/neurotrophin-4 and neurotrophin-3, respectively. Following adrenalectomy no change of tropomyosin receptor kinase B or C messenger RNA was detected in any of the brain regions studied compared to sham-operated animals. The injection of kainic acid caused four-fold and two-fold increases of tropomyosin receptor kinase B messenger RNA in the dentate gyrus and cerebral cortex, respectively, but no change in tropomyosin receptor kinase C messenger RNA in any of these regions. In adrenalectomized animals receiving kainic acid, the level of tropomyosin receptor kinase B messenger RNA was decreased both in the dentate gyrus and cerebral cortex as compared to sham animals treated with kainic acid. Taken together, the data suggest that excitotoxins and glucocorticoids both influence expression of brain-derived neurotrophic factor and nerve growth factor messenger RNA in the brain, but by two different mechanisms, where the effect of excitotoxin-evoked seizures is modulated by glucocorticoids.