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

Karl D Murray, Paul J. Isackson, Thomas A. Eskin, Michael A. King, Sylvia P. Montesinos, Linda A. Abraham, Steven N. Roper

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

The expression of brain-derived neurotrophic factor and the α subunit of calcium/calmodulin-dependent protein kinase II mRNA in hippocampi obtained during surgical resections for intractable temporal lobe epilepsy were examined. Both calcium/calmodulin-dependent protein kinase II and brain- derived neurotrophic factor are localized heavily within the hippocampus and have been 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 morphologic changes typically seen in the epileptic hippocampus. Quantitative assessments of mRNA levels in epileptic hippocampi relative to autopsy controls were made by using normalized densitometric analysis of in situ hybridization. In addition, correlations between clinical data and mRNA levels were studied. Relative to autopsy control tissue, decreased hybridization to mRNA of the α subunit of calcium/calmodulin-dependent protein kinase II and increased hybridization to brain-derived neurotrophic factor mRNA were found throughout the granule cells of the epileptic hippocampus. There also was 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 alterations 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.

Original languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalJournal of Comparative Neurology
Volume418
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

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Keywords

  • Isoforms
  • Neurotrophins
  • Plasticity
  • Regulation
  • Type II calcium/calmodulin-dependent protein kinase

ASJC Scopus subject areas

  • Neuroscience(all)

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