, 2010). Indeed FGF22 has been shown to interact in vitro with both FGFR1b and FGFR2b while FGF7 only interacts with FGFR2b, suggesting that these FGFs control the specificity of presynaptic nerve terminal-postsynaptic target recognition in part through differential binding to FGFR isoforms. Not surprisingly given their widespread involvement in neural development, FGFs have been associated with multiple neurological disorders. Postmortem studies have shown that several FGF ligands and receptors are downregulated in the

prefrontal cortex and hippocampus of patients with major depression, suggesting that dysregulation of FGF Sorafenib datasheet signaling is involved in the disease, e.g., by contributing to the atrophy of the hippocampus and prefrontal cortex reported in depressed patients (Evans et al., 2004 and Riva et al., 2005). A role of FGFs in the action of antidepressants has also been proposed, based on the findings that treating patients and rodents

with specific serotonin reuptake inhibitors increases Fgf expression levels in the prefrontal cortex and Anti-diabetic Compound Library mw other brain regions, and that acute or chronic administration of FGF2 reduces anxiety and depression-like behaviors in rats (Evans et al., 2004, Perez et al., 2009 and Turner et al., 2008). FGF2 could contribute to the action of antidepressants by reversing hippocampal and cortical atrophy as well as through its mitogenic effect on hippocampal progenitors, since some of the behavioral effects of antidepressants require the stimulation of neurogenesis in the adult hippocampus Adenylyl cyclase (Duman and

Monteggia, 2006, Perez et al., 2009 and Zhao et al., 2007). Dysregulation of FGF signaling during development has also been proposed to increase vulnerability to neuropsychiatric disorders such as autism spectrum disorder (ASD) (Rubenstein, 2010 and Vaccarino et al., 2009). According to this hypothesis, mutations in autism susceptibility candidate genes might interfere with FGF signaling and produce defects in brain growth and cortical circuit formation that predispose affected individuals to the disease. This hypothesis has received some support from animal studies, in particular in Fgf17 mutant mice where patterning defects of the frontal cortex during development result in specific deficits in social behaviors and working memory in adults (Scearce-Levie et al., 2008). Besides neuropsychiatric disorders and Kallman syndrome (see above), FGF signaling deficiencies have been implicated in neurodegenerative diseases, including a progressive spinocerebellar ataxia (Laezza et al., 2007 and van Swieten et al., 2003) and Parkinson’s disease (PD).