Journal of Molecular Medicine

, Volume 86, Issue 5, pp 563–571 | Cite as

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

  • Björn Maul
  • Oliver von Bohlen und Halbach
  • Axel Becker
  • Anja Sterner-Kock
  • Jörg-Peter Voigt
  • Wolf-Eberhard Siems
  • Gisela Grecksch
  • Thomas Walther
Original Article

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.

Keywords

Anxiety AT2 receptor Gene deficiency Learning Morris water maze X-linked mental retardation 

Abbreviations

AII

angiotensin II

AT1

angiotensin II type 1 receptor

AT2

angiotensin II type 2 receptor

PSD

postsynaptic densities

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Björn Maul
    • 1
  • Oliver von Bohlen und Halbach
    • 2
  • Axel Becker
    • 3
  • Anja Sterner-Kock
    • 4
  • Jörg-Peter Voigt
    • 5
  • Wolf-Eberhard Siems
    • 1
  • Gisela Grecksch
    • 3
  • Thomas Walther
    • 6
    • 7
  1. 1.Leibniz-Institut für Molekulare PharmakologieBerlinGermany
  2. 2.Interdisciplinary Center for Neurosciences (IZN), Department of NeuroanatomyUniversity of HeidelbergHeidelbergGermany
  3. 3.Institute of Pharmacology and ToxicologyUniversity of MagdeburgMagdeburgGermany
  4. 4.Institute of Pathology, Veterinary MedicineFreie Universität BerlinBerlinGermany
  5. 5.Department of Pharmacology and Toxicology, Veterinary MedicineFreie Universität BerlinBerlinGermany
  6. 6.Department of Cardiology and PneumologyCharité-University Medicine, Campus Benjamin Franklin (CBF)BerlinGermany
  7. 7.Biomedical SciencesHull York Medical SchoolHullUK

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