Altered mRNA expression for brain derived neurotrophic factor and type II calcium/calmodulin-dependent protein kinase in the hippocampus of patients with intractable temporal lobe epilepsy

The expression of brain-derived neurotrophic factor and the cr subunit of c alcium/calmodulin-dependent protein kinase II mRNA in hippocampi obtained d uring surgical resections for intractable temporal lobe epilepsy were exami ned. Both calcium/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor are localized heavily within the hippocampus and have b een implicated in regulating hippocampal activity (Kang and Schuman [1995] Science 267:1658-1662; Suzuki [1994] Intl J Biochem 26:735-744). Also, the autocrine and paracrine actions of brain-derived neurotrophic factor within the central nervous system make it a likely candidate for mediating morpho logic changes typically seen in the epileptic hippocampus. Quantitative ass essments of mRNA levels in epileptic hippocampi relative to autopsy control s were made by using normalized densitometric analysis of in situ hybridiza tion. In addition, correlations between clinical data and mRNA levels were studied. Relative to autopsy control tissue, decreased hybridization to mRN A of the alpha subunit of calcium/calmodulin-dependent protein kinase II an d increased hybridization to brain-derived neurotrophic factor mRNA were fo und throughout the granule cells of the epileptic hippocampus. There also w as a significant negative correlation between the duration of epilepsy and the expression of mRNA for brain-derived neurotrophic factor. These results are similar qualitatively to those found in animal models of epilepsy and suggest that chronic seizure activity in humans leads to persistent alterat ions in gene expression. Furthermore, these alterations in gene expression may play a role in the etiology of the epileptic condition. (C) 2000 Wiley- Liss, Inc.