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 and Jenny Hsieh ()
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Kyung-Ok Cho: UT Southwestern Medical Center
Zane R. Lybrand: UT Southwestern Medical Center
Naoki Ito: UT Southwestern Medical Center
Rebecca Brulet: UT Southwestern Medical Center
Farrah Tafacory: UT Southwestern Medical Center
Ling Zhang: UT Southwestern Medical Center
Levi Good: UT Southwestern Medical Center
Kerstin Ure: Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine
Steven G. Kernie: Columbia University
Shari G. Birnbaum: UT Southwestern Medical Center
Helen E. Scharfman: The Nathan Kline Institute for Psychiatric Research and NYU Langone Medical Center
Amelia J. Eisch: UT Southwestern Medical Center
Jenny Hsieh: UT Southwestern Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7606

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