Fibroblast growth factor as antidepressant: Signaling signatures in different brain areas.

Society for Neuroscience. 2009.


For decades, the pharmacolology of psychiatric disorders has been based in monoamine drug targets. However, current antidepressants produce only a modest improvement (14-18% over placebo). Growing evidence supports that fibroblast growth factor (FGF) ligands may act as endogenous antidepressants. Previous results in our lab show that the FGF system is altered in post-mortem brains of individuals with major depressive disorder, in areas including prefrontal cortex and hippocampus. Our initial hypothesis was further supported by showing in adult rats that acute or chronic FGF-2 administration (200ng, i.c.v.), produce an antidepressant-like effect. Lastly, as expected, the FGF axis was found also altered in an inbred rat model of anxiety and depression. These findings support the potential therapeutic intervention of selected FGF-2 relevant targets in the treatment of depression. However, the molecular basis of the FGF effects in adult brain remain unknown. In this current study we injected rats acutely with FGF-2 and used a broad set of phosphospecific antibodies to characterize signaling patterns in different brain regions . Our results show that acute FGF-2 signals in vivo through at least three main pathways that are typically found altered in depression and regulated by antidepressant and Lithium treatments.