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Epigenetic modulation of seizure-induced neurogenesis and cognitive decline

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dc.contributor.author Sebastian Jessberger ja
dc.contributor.author Kinichi Nakashima ja
dc.contributor.author Gregory D. Clemenson Jr. ja
dc.contributor.author Eunice Mejia ja
dc.contributor.author Emily Mathews ja
dc.contributor.author Kerstin Ure ja
dc.contributor.author Shiori Ogawa ja
dc.contributor.author Christopher M. Sinton ja
dc.contributor.author Fred H. Gage ja
dc.contributor.author Jenny Hsieh ja
dc.date.accessioned 2012-10-03T01:57:34Z
dc.date.available 2012-10-03T01:57:34Z
dc.date.issued 2007-05-30 ja
dc.identifier.issn 0270-6474 ja
dc.identifier.uri http://hdl.handle.net/10061/8563
dc.description.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. ja
dc.language.iso en ja
dc.publisher Society for Neuroscience ja
dc.rights Copyright (C) 2007 Society for Neuroscience. ja
dc.subject valproic acid ja
dc.subject neurogenesis ja
dc.subject hippocampus ja
dc.subject seizure ja
dc.subject object recognition ja
dc.subject learning ja
dc.subject histone deacetylase ja
dc.title Epigenetic modulation of seizure-induced neurogenesis and cognitive decline ja
dc.type.nii Journal Article ja
dc.textversion Publisher ja
dc.identifier.ncid AA10620404 ja
dc.identifier.jtitle Journal of Neuroscience ja
dc.identifier.volume 27 ja
dc.identifier.issue 22 ja
dc.identifier.spage 5967 ja
dc.identifier.epage 5975 ja
dc.relation.doi 10.1523/JNEUROSCI.0110-07.2007 ja

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