INDUCTION OF BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER-RNA BY SEIZURES IN NEONATAL AND JUVENILE RAT-BRAIN

Seizures have been shown to regulate neurotrophin expression in adult mammalian brain. However, there has been some controversy as to whethe r seizures affect neurotrophin expression in very immature brain. In t he present study, we have examined the effects of seizures induced by pilocarpine following lithium pretreatment or by kainic acid on the ex pression of brain derived neurotrophic factor (BDNF) mRNA in developin g rat brain by in situ hybridization. In adult brain, lithium/pilocarp ine treatment resulted in dramatic elevations of hybridization to BDNF cRNA in neocortical and limbic brain structures. In developing brain, lithium/pilocarpine induced elevations of BDNF mRNA in the hippocampu s, piriform and entorhinal cortex as early as postnatal day 7 (P7). By P12, the pattern of enhanced expression was similar to that of the ad ult. Maximal elevations of hybridization were present 2 to 4 h followi ng pilocarpine injection. Electrophysiological recording demonstrated that lithium/pilocarpine treatment resulted in electrographic seizures . Pretreatment with diazepam blocked the seizures as well as the eleva tion of BDNF mRNA. Kainic acid induced elevations of BDNF mRNA in the CA3 subfield of the hippocampal pyramidal cell layer, but not in other brain areas in pups as young as P7. These data indicate that seizures during the neonatal and early juvenile period of brain development in duce elevated BDNF mRNA expression, and that different methods of seiz ure induction yield different patterns of elevations in hybridization. Furthermore, BDNF may be capable of playing a role in the development of seizure susceptibility in the immature brain.