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PMID: 18434527 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Tonic activation of CXC chemokine receptor 4 in immature granule cells supports neurogenesis in the adult dentate gyrus.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 28 ·No. 17 ·2008-04-23 ·Pages 4488-500

Kolodziej A, Schulz S, Guyon A, Wu DF, Pfeiffer M, Odemis V, Höllt V, Stumm R

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.

MeSH Terms
Animals Animals, Newborn Benzylamines Cell Differentiation/drug effects,genetics Cell Line Cells, Cultured Cyclams Dentate Gyrus/cytology,drug effects,growth & development,metabolism Doublecortin Protein Heterocyclic Compounds/agonists,pharmacology Humans Male Neurons/cytology,drug effects,metabolism Rats Rats, Sprague-Dawley Rats, Wistar Receptors, CXCR4/antagonists & inhibitors,biosynthesis,metabolism,physiology Stem Cells/cytology,drug effects,metabolism
Chemicals
Benzylamines Cyclams Dcx protein, rat Doublecortin Protein Heterocyclic Compounds Receptors, CXCR4 plerixafor
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kolodziej Angela
Institut für Pharmakologie und Toxikologie, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany.
Schulz Stefan
Guyon Alice
Wu Dai-Fei
Pfeiffer Manuela
Odemis Veysel
Höllt Volker
Stumm Ralf
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4721-07.2008
Published
2008-04-23
Pages
4488-500
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6670965
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4721-07.2008 PMC Full Text View journal details
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