Journal article
Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors
Biological psychiatry (1969), Vol.80(6), pp.479-489
09/15/2016
DOI: 10.1016/j.biopsych.2016.02.026
PMID: 27133954
Abstract
Despite strong evidence linking fibroblast growth factor 2 (FGF2) with anxiety and depression in both rodents and humans, the molecular mechanisms linking FGF2 with anxiety are not understood.
We compare 1) mice that lack a functional Fgf2 gene (Fgf2 knockout [KO]), 2) wild-type mice, and 3) Fgf2 KO with adult rescue by FGF2 administration on measures of anxiety, depression, and motor behavior, and further investigate the mechanisms of this behavior by cellular, molecular, and neuroendocrine studies.
We demonstrate that Fgf2 KO mice have increased anxiety, decreased hippocampal glucocorticoid receptor (GR) expression, and increased hypothalamic-pituitary-adrenal axis activity. FGF2 administration in adulthood was sufficient to rescue the entire phenotype. Blockade of GR in adult mice treated with FGF2 precluded the therapeutic effects of FGF2 on anxiety behavior, suggesting that GR is necessary for FGF2 to regulate anxiety behavior. The level of Egr-1/NGFI-A was decreased in Fgf2 KO mice and was reestablished with FGF2 treatment. By chromatin immunoprecipitation studies, we found decreased binding of EGR-1 to the GR promoter region in Fgf2 KO mice. Finally, we examined anxiety behavior in FGF receptor (FGFR) KO mice; however, FGFR1, FGFR2, and FGFR3 KO mice did not mimic the phenotype of Fgf2 KO mice, suggesting a role for other receptor subtypes (i.e., FGFR5).
These data suggest that FGF2 levels are critically related to anxiety behavior and hypothalamic-pituitary-adrenal axis activity, likely through modulation of hippocampal glucocorticoid receptor expression, an effect that is likely receptor mediated, albeit not by FGFR1, FGFR2, and FGFR3.
Details
- Title: Subtitle
- Fibroblast Growth Factor 2 Modulates Hypothalamic Pituitary Axis Activity and Anxiety Behavior Through Glucocorticoid Receptors
- Creators
- Natalina Salmaso - Child Study Center, New Haven, ConnecticutHanna E Stevens - Child Study Center, New Haven, ConnecticutJessica McNeill - Department of Neuroscience, Carleton University, Ottawa, Ontario, CanadaMaha ElSayed - Department of Psychiatry, New Haven, ConnecticutQiuyin Ren - Child Study Center, New Haven, ConnecticutMaria E Maragnoli - Child Study Center, New Haven, ConnecticutMichael L Schwartz - Department of Neuroscience, New Haven, ConnecticutSimone Tomasi - Child Study Center, New Haven, ConnecticutRobert M Sapolsky - Departments of Biological Sciences, Neurology, and Neurosurgery, Stanford University, Stanford, CaliforniaRonald Duman - Department of Psychiatry, New Haven, ConnecticutFlora M Vaccarino - Child Study Center, New Haven, Connecticut
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.80(6), pp.479-489
- DOI
- 10.1016/j.biopsych.2016.02.026
- PMID
- 27133954
- NLM abbreviation
- Biol Psychiatry
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Publisher
- Elsevier Inc
- Grant note
- name: FMV, award: R01 MH0677
- Language
- English
- Date published
- 09/15/2016
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984003477002771
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