Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

Kyung Ok Cho, Zane R. Lybrand, Naoki Ito, Rebecca Brulet, Farrah Tafacory, Ling Zhang, Levi Good, Kerstin Ure, Steven G. Kernie, Shari G Birnbaum, Helen E. Scharfman, Amelia J Eisch, Jenny Hsieh

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

Original languageEnglish (US)
Article number6606
JournalNature communications
Volume6
DOIs
StatePublished - Mar 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Cho, K. O., Lybrand, Z. R., Ito, N., Brulet, R., Tafacory, F., Zhang, L., Good, L., Ure, K., Kernie, S. G., Birnbaum, S. G., Scharfman, H. E., Eisch, A. J., & Hsieh, J. (2015). Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nature communications, 6, [6606]. https://doi.org/10.1038/ncomms7606