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Title: Epigenetic modulation of seizure-induced neurogenesis and cognitive decline
Authors: Sebastian Jessberger
Kinichi Nakashima
Gregory D. Clemenson Jr.
Eunice Mejia
Emily Mathews
Kerstin Ure
Shiori Ogawa
Christopher M. Sinton
Fred H. Gage
Jenny Hsieh
Keywords: valproic acid
object recognition
histone deacetylase
Issue Date: 30-May-2007
Publisher: Society for Neuroscience
Journal Title: Journal of Neuroscience
Volume: 27
Issue: 22
Start page: 5967
End page: 5975
Abstract: The conceptual understanding of hippocampal function has been challenged recently by the finding that new granule cells are born throughout life in the mammalian dentate gyrus (DG). The number of newborn neurons is dynamically regulated by a variety of factors. Kainic acid-induced seizures, a rodent model of human temporal lobe epilepsy, strongly induce the proliferation of DG neurogenic progenitor cells and are also associated with long-term cognitive impairment. We show here that the antiepileptic drug valproic acid (VPA) potently blocked seizure-induced neurogenesis, an effect that appeared to be mainly mediated by inhibiting histone deacetylases (HDAC) and normalizing HDAC-dependent gene expression within the epileptic dentate area. Strikingly, the inhibition of aberrant neurogenesis protected the animals from seizure-induced cognitive impairment in a hippocampus-dependent learning task. We propose that seizure-generated granule cells have the potential to interfere with hippocampal function and contribute to cognitive impairment caused by epileptic activity within the hippocampal circuitry. Furthermore, our data indicate that the effectiveness of VPA as an antiepileptic drug may be partially explained by the HDAC-dependent inhibition of aberrant neurogenesis induced by seizure activity within the adult hippocampus.
ISSN: 0270-6474
Rights: Copyright (C) 2007 Society for Neuroscience.
Text Version: Publisher
Publisher DOI: 10.1523/JNEUROSCI.0110-07.2007
Appears in Collections:バイオサイエンス研究科 / Graduate School of Biological Sciences

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