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The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopressin neurons and counteracts induced vasopressin release through CXCR4

  1. Céline Callewaere * , † , ‡ ,
  2. Ghazal Banisadr * , † , ‡ ,
  3. Michel G. Desarménien § , ¶, , ‖ ,
  4. Patricia Mechighel * , † ,
  5. Patrick Kitabgi * , † ,
  6. William H. Rostène * , † , **, and
  7. Stéphane Mélik Parsadaniantz * , †
  1. *Institut National de la Santé et de la Recherche Médicale, Unité 732, F-75012 Paris, France;
  2. †Université Pierre et Marie Curie-Paris 6, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, F-75571 Paris Cedex 12, France;
  3. §Institut de Génomique Fonctionnelle, Université Montpellier, Faculté de Médecine, F-34094 Montepellier, France;
  4. Institut National de la Santé et de la Recherche Médicale, Unité 661, F-34094 Montpellier, France; and
  5. ‖Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, F-34094 Montpellier, France

  1. Communicated by Bruce S. McEwen, The Rockefeller University, New York, NY, April 3, 2006

  2. ↵ ‡C.C. and G.B. contributed equally to this work. (received for review December 12, 2005)

Abstract

Chemokines play a key role in inflammation. They are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types, including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. Here, we investigated a possible neuroendocrine role of the chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12. We demonstrated the colocalization of SDF-1 and its receptor CXCR4 with arginine vasopressin (AVP) in the magnocellular neurons of the supraoptic nucleus (SON) and the paraventricular hypothalamic nucleus and on AVP projections to the neurohypophysis. Electrophysiological recordings of SON neurons demonstrated that SDF-1 affects the electrical activity of AVP neurons through CXCR4, resulting in changes in AVP release. We observed that SDF-1 can blunt the autoregulation of AVP release in vitro and counteract angiotensin II-induced plasma AVP release in vivo. Furthermore, a short-term physiological increase in AVP release induced by enhanced plasma osmolarity, which was produced by the administration of 1 M NaCl i.p., was similarly blocked by central injection of SDF-1 through CXCR4. A change in water balance by long-term salt loading induced a decrease in both SDF-1 and CXCR4 parallel to that of AVP immunostaining in SON. From these data, we demonstrate that chemokine actions in the brain are not restricted to inflammatory processes. We propose to add to the known autoregulation of AVP on its own neurons, a second autocrine system induced by SDF-1 able to modulate central AVP neuronal activity and release.

Footnotes

  • **To whom correspondence should be addressed. E-mail: rostene{at}st-antoine.inserm.fr

  • Author contributions: W.H.R. and S.M.P. designed research; C.C., G.B., M.G.D., P.M., W.H.R., and S.M.P. performed research; and W.H.R., P.K., and S.M.P. wrote the paper.

  • Conflict of interest statement: No conflicts declared.

  • Abbreviations:

    Abbreviations:

    AII,
    angiotensin II;
    aCSF,
    artificial cerebrospinal fluid;
    AMD,
    AMD3100 (bicyclam);
    AVP,
    arginine vasopressin;
    CVO,
    circumventricular organ;
    ISI,
    interspike interval;
    OT,
    oxytocin;
    PVN,
    hypothalamic paraventricular nucleus;
    SDF-1,
    stromal cell-derived factor 1;
    SON,
    hypothalamic supraoptic nucleus.

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