Abstract

Increased fibroblast growth factor-12 (FGF12) is associated with negative affect

Turner CA, Waselus M, O'Connor AM, Krolewski DM, Foltz M, Kumar V, Lee FS, Bunney R, Bunney WE, Bunney B, Schatzberg AF, Barchas JD, Watson SJ, Akil H
51st Annual Meeting of the Society for Neuroscience. 2022.

The fibroblast growth factor (FGF) family has previously been implicated in mood disorders, especially Major Depressive Disorder (MDD). FGF12, one of the intracellular members, was increased in the anterior cingulate cortex of individuals with MDD (Evans et al., 2004). FGF12 is an intracellular FGF that binds to voltage-gated sodium channels to increase neuronal excitability. We sought to understand whether FGF12 was altered in the hippocampus of individuals with mood disorders, particularly MDD. We also analyzed FGF12 gene expression in the hippocampus of two rodent models of depression-like behavior. Finally, we sought to determine cell type expression of FGF12. In MDD, FGF12 gene expression was increased in the postmortem human hippocampus by qRT-PCR, and the anterior dentate gyrus by mRNA in situ hybridization. In rats, FGF12 gene expression was increased in the dentate gyrus of the hippocampus following chronic variable stress and subchronic social defeat in adulthood. FGF12 mRNA was present in glutamatergic and all subtypes of GABAergic neurons in the cortex and the dentate gyrus. Since intracellular FGF12 can increase neuronal excitability through its interaction with voltage-gated sodium channels, and there are considerably more glutamatergic cells in the dentate gyrus, FGF12 may bias the hippocampus towards increased excitability. This hypothesis remains to be tested. In conclusion, increased FGF12 is associated with depression in humans and stress exposure in rodents. Its potential role in altered excitation-inhibition balance in the hippocampus warrants further investigation.