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Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

Author

Listed:
  • Kyung-Ok Cho

    (UT Southwestern Medical Center
    School of Medicine, The Catholic University of Korea)

  • Zane R. Lybrand

    (UT Southwestern Medical Center)

  • Naoki Ito

    (UT Southwestern Medical Center
    Oriental Medicine Research Center, Kitasato University)

  • 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)

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.

Suggested Citation

  • 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 & Jen, 2015. "Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7606
    DOI: 10.1038/ncomms7606
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