Epigenetic Modulation of Seizure-Induced Neurogenesis and Cognitive Decline

By Sebastian Jessberger, K. Nakashima, Gregory D. Clemenson, Eunice Mejia, Emily Mathews, Kerstin Ure, Shiori Ogawa, C. Sinton, Fred H. Gage, Jenny Hsieh. 2007

363 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Developmental Neuroscience

1. Fred H. Gage
2. Hongjun Song
3. Sebastian Jessberger
4. Chunmei Zhao
5. Gregory D. Clemenson
6. Guo-li Ming
7. D. C. Lie
8. Yan Li

In Molecular Biology

1. Hongjun Song
2. Fred H. Gage
3. D. C. Lie
4. Sebastian Jessberger
5. Yan Li
6. Chunmei Zhao
7. Guo-li Ming

Citations in the corpus

• Seizure-Associated, Aberrant Neurogenesis in Adult Rats Characterized with Retrovirus-Mediated Cell Labeling (2007, methodology): “This time period is when proliferation of neural progenitors in the SGZ of female rats is massively elevated (Jessberger et al., 2007).”
• GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus (2009, background): “Adult hippocampal neurogenesis may represent a candidate target process for the treatment of age-related cognitive decline (Drapeau and Nora Abrous, 2008), seizure-induced cognitive impairment (Jakubs et al., 2006; Jessberger et al., 2007), and mood disorders (Duman, 2004; Sahay and Hen, 2008).”