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Fibroblast Growth Factor 2 Sits at the Interface of Stress and Anxiety

  • Cortney A. Turner
    Correspondence
    Address correspondence to Cortney A. Turner, University of Michigan, Molecular and Behavioral Neuroscience Institute, 205 Zina Pitcher Place, Ann Arbor, MI 48109.
    Affiliations
    Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan

    Department of Psychiatry, University of Michigan, Ann Arbor, Michigan
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  • Stanley J. Watson
    Affiliations
    Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan

    Department of Psychiatry, University of Michigan, Ann Arbor, Michigan
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  • Huda Akil
    Affiliations
    Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan

    Department of Psychiatry, University of Michigan, Ann Arbor, Michigan
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      The role of growth factors in the control of mood and emotions has gained considerable interest. In particular, discoveries during the past decade have pointed to the involvement of the fibroblast growth factor (FGF) family in affect regulation and have underscored the ability of one member, FGF2, to decrease depression and anxiety behaviors in animal models (
      • Turner C.A.
      • Watson S.J.
      • Akil H.
      The fibroblast growth factor family: Neuromodulation of affective behavior.
      ). In the present report, Salmaso et al. (
      • Salmaso N.
      • Stevens H.E.
      • McNeill J.
      • ElSayed M.
      • Ren Q.
      • Maragnoli M.E.
      • et al.
      Fibroblast growth factor 2 modulates hypothalamic pituitary axis activity and anxiety behavior through glucocorticoid receptors.
      ) show that Fgf2 knockout (KO) mice exhibit increased anxiety behavior, and this phenotype is rescued by FGF2 administration in adulthood (
      • Salmaso N.
      • Stevens H.E.
      • McNeill J.
      • ElSayed M.
      • Ren Q.
      • Maragnoli M.E.
      • et al.
      Fibroblast growth factor 2 modulates hypothalamic pituitary axis activity and anxiety behavior through glucocorticoid receptors.
      ). The Fgf2 KO mice also have decreased glucocorticoid receptor (GR) expression in the hippocampus that is associated with increased hypothalamic-pituitary-adrenal (HPA) axis activity. When the authors blocked GR with RU486, FGF2 was no longer effective on anxiety behavior in the KO mice. The authors suggest that GR is necessary for the anxiety-reducing actions of FGF2. They propose the transcription factor early growth response protein 1 as a potential mediator, because early growth response protein 1 was decreased in Fgf2 KO mice, rescued by the FGF2 treatment, and associated with the GR promoter in Fgf2 KO mice. Their interesting findings on the role of FGF2 in this model support and strengthen the literature on the role of this factor in controlling affect. Their conclusions on the role of GR in mediating the effects of FGF2 are novel and interesting, but their conclusions need to be discussed in the context of the complex and often bimodal actions of GR, stress, and anxiety regulation.
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