Antidepressant Effects of Fibroblast Growth Factor-2 in Behavioral and Cellular Models of Depression
Open accessAbstract
Background Basic and clinical studies report that the expression of fibroblast growth factor-2 (FGF-2) is decreased in the prefrontal cortex (PFC) of depressed subjects or rodents exposed to stress and increased following antidepressant treatment. Here, we aim to determine if 1) FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for mediating an antidepressant response behaviorally and cellularly; and 2) if the antidepressant actions of FGF-2 are mediated specifically by the PFC.Methods The role of FGF-2 signaling in behavioral models of depression and anxiety was tested using chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), and novelty suppressed feeding test (NSFT). We also assessed the number of bromodeoxyuridine labeled dividing glial cells in the PFC as a cellular index relevant to depression (i.e., decreased by stress and increased by antidepressant treatment).Results Chronic FGF-2 infusions (intracerebroventricular) blocked the deficit in SCT caused by CUS. Moreover, the response to antidepressant treatment in the CUS/SCT and FST was abolished upon administration of an inhibitor of FGFR activity, SU5402. These results are consistent with the regulation of proliferating cells in the PFC, a portion of which are of oligodendrocyte lineage. Lastly, subchronic infusions of FGF-2 into the PFC but not into the dorsal striatum produced antidepressant-like and anxiolytic-like effects on FST and NSFT respectively.Conclusions These findings demonstrate that FGF-2/FGFR signaling is sufficient and necessary for the behavioral, as well as gliogenic, actions of antidepressants and highlight the PFC as a brain region sensitive to the antidepressant actions of FGF-2.
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Increased cell proliferation in the PFC following FGF2 infusions might be involved in the antidepressant actions of FGF2.
“A more recent study also reported that increased cell proliferation in the PFC following FGF2 infusions might also be involved in the antidepressant actions of FGF2 (Elsayed et al. 2012).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Elsayed et al. 2012
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- Authors
- Elsayed, M., Banasr, M., Duric, V., Fournier, N. M., Licznerski, P., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Duman, Ronald S.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 72
- Issue
- 4
- Pages
- 258-265
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3401338
- OpenAlex
- W2087978290
- Cited by
- 169
- References
- 66
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 16 · 2018: 12 · 2017: 17 · 2016: 11 · 2015: 17 · 2014: 10 · 2013: 13 · 2012: 8
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R37MH45481, R37MH045481, R01MH045481)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- fibroblast growth factor 2, FGFR signaling, antidepressant effects, depression, prefrontal cortex, chronic unpredictable mild stress, SU5402, bromodeoxyuridine, glial cell proliferation, oligodendrocyte lineage, anxiolytic effects, forced swim test
- MeSH terms
- Analysis of Variance, Animals, Antidepressive Agents, Bromodeoxyuridine, Depressive Disorder, Disease Models, Animal, Fluoxetine, Imipramine, Immunohistochemistry, Male, Mice, Inbred C57BL, Neuroglia, Pyrroles, Stress, Psychological, Fibroblast Growth Factor 2, Rats, Sprague-Dawley, Prefrontal Cortex, Receptors, Fibroblast Growth Factor, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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