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Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels

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Abstract

Mice mutant for the presynaptic protein Bassoon develop epileptic seizures and an altered pattern of neuronal activity that is accompanied by abnormal enlargement of several brain structures, with the strongest size increase in hippocampus and cortex. Using manganese-enhanced magnetic resonance imaging, an abnormal brain enlargement was found, which is first detected in the hippocampus 1 month after birth and amounts to an almost 40% size increase of this structure after 3 months. Stereological quantification of cell numbers revealed that enlargement of the dentate gyrus and the hippocampus proper is associated with larger numbers of principal neurons and of astrocytes. In search for the underlying mechanisms, an approximately 3-fold higher proportion of proliferation and survival of new-born cells in the dentate gyrus was found to go hand in hand with similarly larger numbers of doublecortin-positive cells and reduced numbers of apoptotic cells in the dentate gyrus and the hippocampus proper. Enlargement of the hippocampus and of other forebrain structures was accompanied by increased levels of brain-derived neurotrophic factor (BDNF). These data show that hippocampal overgrowth in Bassoon-mutant mice arises from a dysregulation of neurogenesis and apoptosis that might be associated with unbalanced BDNF levels.

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Acknowledgements

We wish to thank Kathrin Baldauf, Eike Budinger, Anna Fejtova, Jürgen Goldschmidt, Gisela Grecksch, Thomas Roskoden and Henning Scheich for advice and many helpful discussions. We thank Yves-Alain Barde for support and highly valuable comments on the manuscript. We are grateful to Kathrin Gruss, Karla Krautwald, and Kathrin Pohlmann for expert technical assistance.

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Authors and Affiliations

  1. Department for Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118, Magdeburg, Germany

    Alexandra Heyden, Stefano Romorini, Bettina Kracht, Constanze Seidenbecher & Eckart D. Gundelfinger

  2. Leibniz Institute for Neurobiology, Special Lab Non-invasive Brain Imaging, Brenneckestr. 6, 39118, Magdeburg, Germany

    Frank Angenstein

  3. Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany

    Alexandra Heyden

  4. Biozentrum, University of Basel, Klingelbergstr. 50/70, Basel, CH-4056, Switzerland

    Mihai-Constantin S. Ionescu

  5. Laboratorio di Neurofisiologia, Fondazione Santa Lucia, IRCCS, Rome, Italy

    Veronica Ghiglieri & Paolo Calabresi

  6. Department of Neurology, University of Magdeburg, Magdeburg, Germany

    Frank Angenstein

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  1. Alexandra Heyden
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  2. Mihai-Constantin S. Ionescu
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  9. Eckart D. Gundelfinger
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Correspondence to Frank Angenstein.

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This work was supported by the Pakt für Forschung und Innovation of the Leibniz Society, the Deutsche Forschungsgemeinschaft (SFB 779) and the EC contract number 222918 (REPLACES) FP7 - Thematic priority HEALTH.

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Heyden, A., Ionescu, MC.S., Romorini, S. et al. Hippocampal enlargement in Bassoon-mutant mice is associated with enhanced neurogenesis, reduced apoptosis, and abnormal BDNF levels. Cell Tissue Res 346, 11–26 (2011). https://doi.org/10.1007/s00441-011-1233-3

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