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Impaired spatial memory and altered dendritic spine morphology in angiotensin II type 2 receptor-deficient mice

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Abstract

Mental retardation is the most frequent cause of serious handicap in children and young adults. Mutations in the human angiotensin II type 2 receptor (AT2) have been implicated in X-linked forms of mental retardation. We here demonstrate that mice lacking the AT2 receptor gene are significantly impaired in their performance in a spatial memory task and in a one-way active avoidance task. As no difference was observed between the genotypes in fear conditioning, the detected deficit in spatial memory may not relate to fear. Notably, receptor knockout mice showed increased motility in an activity meter and elevated plus maze. Importantly, these mice are characterized by abnormal dendritic spine morphology and length, both features also found to be associated with some cases of mental retardation. These findings suggest a crucial role of AT2 in normal brain function and that dysfunction of the receptor has impact on brain development and ultrastructural morphology with distinct consequences on learning and memory.

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Abbreviations

AII :

angiotensin II

AT1 :

angiotensin II type 1 receptor

AT2 :

angiotensin II type 2 receptor

PSD :

postsynaptic densities

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Author notes

  1. Thomas Walther

    Present address: Biomedical Sciences, Hull York Medical School, Hull, UK

Authors and Affiliations

  1. Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany

    Björn Maul & Wolf-Eberhard Siems

  2. Interdisciplinary Center for Neurosciences (IZN), Department of Neuroanatomy, University of Heidelberg, Heidelberg, Germany

    Oliver von Bohlen und Halbach

  3. Institute of Pharmacology and Toxicology, University of Magdeburg, Magdeburg, Germany

    Axel Becker & Gisela Grecksch

  4. Institute of Pathology, Veterinary Medicine, Freie Universität Berlin, Berlin, Germany

    Anja Sterner-Kock

  5. Department of Pharmacology and Toxicology, Veterinary Medicine, Freie Universität Berlin, Berlin, Germany

    Jörg-Peter Voigt

  6. Department of Cardiology and Pneumology, Charité-University Medicine, Campus Benjamin Franklin (CBF), Hindenburgdamm 30, 12200, Berlin, Germany

    Thomas Walther

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  1. Björn Maul
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Correspondence to Thomas Walther.

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Maul, B., von Bohlen und Halbach, O., Becker, A. et al. Impaired spatial memory and altered dendritic spine morphology in angiotensin II type 2 receptor-deficient mice. J Mol Med 86, 563–571 (2008). https://doi.org/10.1007/s00109-008-0316-4

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  • DOI: https://doi.org/10.1007/s00109-008-0316-4

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