Cho Kyung-Ok, Lybrand Zane R, Ito Naoki, Brulet Rebecca, Tafacory Farrah, Zhang Ling, Good Levi, Ure Kerstin, Kernie Steven G, Birnbaum Shari G, Scharfman Helen E, Eisch Amelia J, Hsieh Jenny
1] Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Pharmacology, School of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
Nat Commun. 2015 Mar 26;6:6606. doi: 10.1038/ncomms7606.
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.
严重脑损伤后急性发作常可导致癫痫和认知障碍。损伤后海马神经发生异常,但成年后生成的神经元在慢性癫痫发作或相关认知缺陷发展中的作用仍有待确定。在此,我们表明,在毛果芸香碱诱导的小鼠急性发作前消除成年神经发生,可导致慢性癫痫发作频率降低。我们还表明,消除神经发生可使癫痫相关的认知缺陷恢复正常。值得注意的是,在急性发作前消除成年神经发生的效果持久,因为它可抑制慢性癫痫发作频率近1年。这些发现确立了神经发生在慢性癫痫发作发展及相关记忆障碍中的关键作用,并表明针对异常海马神经发生可能减少癫痫复发,并在癫痫性脑损伤后恢复认知功能。