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Experimental epilepsy affects Notch1 signalling and the stem cell pool in the dentate gyrus

  1. Mirjam Sibbe1,*,
  2. Ute Häussler2,
  3. Sandra Dieni1,
  4. Daniel Althof1,3,4,
  5. Carola A. Haas2,
  6. Michael Frotscher1,5,*

Article first published online: 17 SEP 2012

DOI: 10.1111/j.1460-9568.2012.08279.x

Issue

European Journal of Neuroscience

European Journal of Neuroscience

Volume 36, Issue 12, pages 3643–3652, December 2012

Additional Information

How to Cite

Sibbe, M., Häussler, U., Dieni, S., Althof, D., Haas, C. A. and Frotscher, M. (2012), Experimental epilepsy affects Notch1 signalling and the stem cell pool in the dentate gyrus. European Journal of Neuroscience, 36: 3643–3652. doi: 10.1111/j.1460-9568.2012.08279.x

Author Information

  1. 1

    Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany

  2. 2

    Experimental Epilepsy Research, Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany

  3. 3

    Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany

  4. 4

    Faculty of Biology, University of Freiburg, Freiburg, Germany

  5. 5

    Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg, Hamburg, Germany

* Correspondence: Mirjam Sibbe, 1Institute of Anatomy and Cell Biology, as above.
E-mail: Mirjam.Sibbe@anat.uni-freiburg.de
or
Michael Frotscher, 5Institute for Structural Neurobiology, as above.
E-mail: Michael.Frotscher@zmnh.uni-hamburg.de

Publication History

  1. Issue published online: 17 DEC 2012
  2. Article first published online: 17 SEP 2012
  3. Manuscript Accepted: 9 AUG 2012
  4. Manuscript Revised: 25 JUL 2012
  5. Manuscript Received: 7 NOV 2011

Funded by

  • Deutsche Forschungsgemeinschaft
  • Excellence Initiative of the German Federal and State Governments GSC-4
  • Spemann Graduate School
  • Hertie Foundation

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Keywords:

  • dentate gyrus;
  • mouse hippocampus;
  • neuronal differentiation;
  • neuronal migration;
  • stem cell niche

Abstract

Temporal lobe epilepsy (TLE) is the most frequent form of epilepsy in adults. In addition to recurrent focal seizures, patients suffer from memory loss and depression. The factors contributing to these symptoms are unknown. In recent years, adult hippocampal neurogenesis has been implicated in certain aspects of learning and memory, as well as in depression and anhedonia. Here we investigated whether the adult hippocampal stem cell niche is affected by status epilepticus in a mouse model of TLE using unilateral intrahippocampal kainic acid injection. Eight days after status epilepticus, we found a strong diminution in Notch signalling, a key pathway involved in stem cell maintenance, as assayed by hes5 reporter gene activity. In particular, hes5–GFP expression in the subgranular zone of the dentate gyrus was diminished. Furthermore, Sox2-positive cells as well as stem cell proliferation were reduced, thus pointing to a disruption of the stem cell niche in epilepsy under the present experimental conditions.

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