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Reduced secretagogin expression in the hippocampus of P301L tau transgenic mice

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Neuropathological features in Alzheimer’s Disease (AD) include the presence of hyperphosphorylated forms of the microtubule-associated tau protein (tau) in hippocampal neurones. Numerous studies indicate a neuroprotective effect of calcium-binding proteins (Ca2+ binding proteins) in neurodegenerative diseases (e.g., AD). Secretagogin is a newly described Ca2+ binding protein that is produced by pyramidal neurones of the human hippocampus. Recently, secretagogin expressing hippocampal neurones were demonstrated to resist tau-induced pathology in AD in contrast to the majority of neighbouring neurones. This suggested a neuroprotective effect of secretagogin in hippocampal neurones. Here, we investigated secretagogin expression in wild type (wt) mice as well as in hemizygous and homozygous P301L tau transgenic (tg) mice, which show pronounced and widespread tau pathology in hippocampal neurones. Secretagogin expression was analyzed at the immunohistochemical and biochemical levels in brains of age-matched wt and hemi- and homozygous tau tg mice. In wt mice hippocampal secretagogin-immunoreactive neurones were invariably detected, while immunoreactivity was much lower (P < 0.001) in tau tg mice. Of note, hippocampal secretagogin immunoreactivity was absent in 62.5% of homozygous tau tg mice. In line with this finding, Western blot analysis demonstrated a significant reduction in protein expression levels of secretagogin in homozygous tau tg compared to wt mice. Our results suggest that increased levels of tau negatively influence secretagogin expression in the hippocampus of tau tg mice.

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Acknowledgments

This work was supported by the Newcastle NIHR Biomedical Research Centre In Ageing and Age Related Diseases, the Alzheimer Research Trust (ART-EG2010A-1) and by the Medical Scientific Fund of the Mayor of the City of Vienna (Grant number 08052). Mathias Heikenwalder was supported by the Prof. Dr. Max-Cloëtta foundation, the Hofschneider Stiftung and the Helmholtz-Zentrum München. The authors thank Ms. Barbara Weidinger for excellent laboratory work.

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Authors and Affiliations

  1. Institute for Ageing and Health, Wolfson Research Centre, Newcastle University, NE4 5PL, Newcastle upon Tyne, UK

    Johannes Attems

  2. Alzheimer’s and Parkinson’s Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, 100 Mallett Street, Camperdown, NSW, 2050, Australia

    Arne Ittner & Jürgen Götz

  3. Institute for Clinical Neurobiology, Kenyongasse 18, 1070, Vienna, Austria

    Kurt Jellinger

  4. Division for Psychiatry Research, University Hospital Zürich, August Forel Strasse 1, 8008, Zürich, Switzerland

    Roger M. Nitsch

  5. Departement of Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Magdalena Maj & Ludwig Wagner

  6. Institute for Virology, Technische Universität München (TUM), Helmholtz Zentrum München (HMGU) Schneckenburgstrasse 8, 81675, München, Germany

    Mathias Heikenwalder

  7. Institute for Neuropathology, University Hospital Zürich, Schmelzbergstrasse 12, 8091, Zürich, Switzerland

    Mathias Heikenwalder

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  1. Johannes Attems
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  2. Arne Ittner
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Correspondence to Johannes Attems.

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Attems, J., Ittner, A., Jellinger, K. et al. Reduced secretagogin expression in the hippocampus of P301L tau transgenic mice. J Neural Transm 118, 737–745 (2011). https://doi.org/10.1007/s00702-011-0626-5

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  • DOI: https://doi.org/10.1007/s00702-011-0626-5

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