Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

异常海马神经发生导致癫痫和相关的认知能力下降

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作者: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

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.

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