Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cognition Disorders / chemically induced
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology*
  • Disease Models, Animal
  • Epilepsy / chemically induced
  • Epilepsy / complications
  • Epilepsy / physiopathology
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / complications
  • Epilepsy, Temporal Lobe / physiopathology*
  • Hippocampus / growth & development*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Muscarinic Agonists / toxicity
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells
  • Neurogenesis / genetics*
  • Neurogenesis / physiology
  • Neurons / metabolism
  • Neuropeptides / metabolism
  • Pilocarpine / toxicity

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Microtubule-Associated Proteins
  • Muscarinic Agonists
  • Nerve Tissue Proteins
  • Neuropeptides
  • doublecortin protein
  • Pilocarpine
  • NeuroD protein