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      Tonic Activation of CXC Chemokine Receptor 4 in Immature Granule Cells Supports Neurogenesis in the Adult Dentate Gyrus

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          Abstract

          Stromal-cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) play a well-established role during embryonic development of dentate gyrus granule cells. However, little is known about the regulation and function of CXCR4 in the postnatal dentate gyrus. Here, we identify a striking mismatch between intense CXCR4 mRNA and limited CXCR4 protein expression in adult rat subgranular layer (SGL) neurons. We demonstrate that CXCR4 protein expression in SGL neurons is progressively lost during postnatal day 15 (P15) to P21. This loss of CXCR4 protein expression was paralleled by a reduction in the number of SDF-1-responsive SGL neurons and a massive upregulation of SDF-1 mRNA in granule cells. Intraventricular infusion of the CXCR4-antagonist AMD3100 dramatically increased CXCR4 protein expression in SGL neurons, suggesting that CXCR4 is tonically activated and downregulated by endogenous SDF-1. Infusion of AMD3100 also facilitated detection of CXCR4 protein in bromodeoxyuridine-, nestin-, and doublecortin-labeled cells and showed that the vast majority of adult-born granule cells transiently expressed CXCR4. Chronic AMD3100 administration impaired formation of new granule cells as well as neurogenesis-dependent long-term recognition of novel objects. Therefore, our findings suggest that tonic activation of CXCR4 in newly formed granule cells by endogenous SDF-1 is essential for neurogenesis-dependent long-term memory in the adult hippocampus.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          23 April 2008
          : 28
          : 17
          : 4488-4500
          Affiliations
          [1] 1Institut für Pharmakologie und Toxikologie, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany,
          [2] 2Insitut für Pharmakologie und Toxikologie, Friedrich-Schiller-University, 07743 Jena, Germany,
          [3] 3Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia Antipolis–Centre National de la Recherche Scientifique, 06560 Valbonne, France, and
          [4] 4Institut für Anatomie, University of Leipzig, 04103 Leipzig, Germany
          Author notes
          Correspondence should be addressed to Dr. Ralf Stumm, Institut für Pharmakologie und Toxikologie, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. ralf.stumm@ 123456medizin.uni-magdeburg.de
          Article
          PMC6670965 PMC6670965 6670965 3338906
          10.1523/JNEUROSCI.4721-07.2008
          6670965
          18434527
          b8f18406-042c-445a-a067-02b31c17dbc2
          Copyright © 2008 Society for Neuroscience 0270-6474/08/284488-13$15.00/0
          History
          : 13 July 2007
          : 15 February 2007
          : 25 February 2008
          Categories
          Articles
          Development/Plasticity/Repair

          neurogenesis,memory,Akt,internalization,hippocampus,desensitization,CXCL12

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