Cited by 169Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorNeurogenesis and neuroplasticity mechanisms

Antidepressant Effects of Fibroblast Growth Factor-2 in Behavioral and Cellular Models of Depression

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Elsayed, Maha, Banasr, Mounira, Duric, Vanja, Fournier, Neil M., Licznerski, Pawel, Duman, Ronald S.·2012·Biological Psychiatry

Abstract

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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Crossref · 10.1016/j.biopsych.2012.03.003

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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)
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
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

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