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

133 Citations (Scopus)

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 - 2015

Fingerprint

epilepsy
seizures
Neurogenesis
Ablation
Epilepsy
Brain
Seizures
Pilocarpine
Neurons
Data storage equipment
impairment
ablation
brain
pilocarpine
Cognitive Dysfunction
neurons
Cognition
mice

ASJC Scopus subject areas

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

Cite this

Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. / 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.

In: Nature Communications, Vol. 6, 6606, 2015.

Research output: Contribution to journalArticle

Cho, KO, Lybrand, ZR, Ito, N, Brulet, R, Tafacory, F, Zhang, L, Good, L, Ure, K, Kernie, SG, Birnbaum, SG, Scharfman, HE, Eisch, AJ & Hsieh, J 2015, 'Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline', Nature Communications, vol. 6, 6606. https://doi.org/10.1038/ncomms7606
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. / Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. In: Nature Communications. 2015 ; Vol. 6.
@article{adc3b80d38cf4eb3b9fe8e7356ed2ed8,
title = "Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline",
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.",
author = "Cho, {Kyung Ok} and Lybrand, {Zane R.} and Naoki Ito and Rebecca Brulet and Farrah Tafacory and Ling Zhang and Levi Good and Kerstin Ure and Kernie, {Steven G.} and Birnbaum, {Shari G} and Scharfman, {Helen E.} and Eisch, {Amelia J} and Jenny Hsieh",
year = "2015",
doi = "10.1038/ncomms7606",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

AU - Cho, Kyung Ok

AU - Lybrand, Zane R.

AU - Ito, Naoki

AU - Brulet, Rebecca

AU - Tafacory, Farrah

AU - Zhang, Ling

AU - Good, Levi

AU - Ure, Kerstin

AU - Kernie, Steven G.

AU - Birnbaum, Shari G

AU - Scharfman, Helen E.

AU - Eisch, Amelia J

AU - Hsieh, Jenny

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925777847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925777847&partnerID=8YFLogxK

U2 - 10.1038/ncomms7606

DO - 10.1038/ncomms7606

M3 - Article

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 6606

ER -