TY - JOUR T1 - Epigenetic Modulation of Seizure-Induced Neurogenesis and Cognitive Decline JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5967 LP - 5975 DO - 10.1523/JNEUROSCI.0110-07.2007 VL - 27 IS - 22 AU - Sebastian Jessberger AU - Kinichi Nakashima AU - Gregory D. Clemenson, Jr AU - Eunice Mejia AU - Emily Mathews AU - Kerstin Ure AU - Shiori Ogawa AU - Christopher M. Sinton AU - Fred H. Gage AU - Jenny Hsieh Y1 - 2007/05/30 UR - http://www.jneurosci.org/content/27/22/5967.abstract N2 - 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. ER -