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.
authors: 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.
authors: Kyung-Ok
authors: KO
authors: Cho
authors: Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Zane R
authors: ZR
authors: Lybrand
authors: 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.
authors: Naoki
authors: N
authors: Ito
authors: Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Rebecca
authors: R
authors: Brulet
authors: Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Farrah
authors: F
authors: Tafacory
authors: Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Ling
authors: L
authors: Zhang
authors: Department of Neurology &Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Levi
authors: L
authors: Good
authors: Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Kerstin
authors: K
authors: Ure
authors: Department of Pediatrics, Columbia University, New York, New York 10027, USA.
authors: Steven G
authors: SG
authors: Kernie
authors: Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Shari G
authors: SG
authors: Birnbaum
authors: The Nathan Kline Institute for Psychiatric Research and NYU Langone Medical Center, Orangeburg, New York 10962, USA.
authors: Helen E
authors: HE
authors: Scharfman
authors: Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Amelia J
authors: AJ
authors: Eisch
authors: Department of Molecular Biology and Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Jenny
authors: J
authors: Hsieh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018721:Muscarinic Agonists / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D018721:Muscarinic Agonists; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010862:Pilocarpine; C093564:Neurogenic differentiation factor 1