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Nat Commun. 2015 Mar 26;6:6606. doi: 10.1038/ncomms7606.

Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

Author information

1
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.
2
Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
3
1] Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Clinical Research, Oriental Medicine Research Center, Kitasato University, Tokyo 108-8641, Japan.
4
Department of Neurology &Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
5
Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and Baylor College of Medicine, Houston, Texas 77030, USA.
6
Department of Pediatrics, Columbia University, New York, New York 10027, USA.
7
Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
8
The Nathan Kline Institute for Psychiatric Research and NYU Langone Medical Center, Orangeburg, New York 10962, USA.

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.

PMID:
25808087
PMCID:
PMC4375780
DOI:
10.1038/ncomms7606
[Indexed for MEDLINE]
Free PMC Article

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