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

Authors

  • Mirjam Sibbe,

    Corresponding author
    • Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
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  • Ute Häussler,

    1. Experimental Epilepsy Research, Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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  • Sandra Dieni,

    1. Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
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  • Daniel Althof,

    1. Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
    2. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
    3. Faculty of Biology, University of Freiburg, Freiburg, Germany
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  • Carola A. Haas,

    1. Experimental Epilepsy Research, Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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  • Michael Frotscher

    Corresponding author
    1. Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg, Hamburg, Germany
    • Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany
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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

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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