FGF2 and chronic stress alter exon-specific expression of FGFR2 and FGFR3
J. S. LIU; C. A. TURNER; A. J. OSETEK; L. P. TAYLOR; H. AKIL; S. J. WATSON; S. J. EVANS
Society for Neuroscience. 2007.
The fibroblast growth factor (FGF) system is important for development and maintenance of the nervous system. Previous studies have shown that several FGF system transcripts are altered in post-mortem brains of major depressive subjects, including a decreased expression of FGFR2 and FGFR3. Each of these receptors has multiple splice variants, including the IIIc and IIIb variants that have unique pharmacological profiles. In the current study we evaluate the exon-specific transcriptional control of FGFR2 and FGFR3 in the rodent frontal cortex following either chronic administration of FGF2, chronic exposure to unpredictable stress or both. Our studies indicate that FGF2 injection non-specifically increases expression of FGFR2 exons and that both chronic unpredictable stress (CUS) and FGF2 injection non-specifically decreases expression of FGFR3 exons. Furthermore, our studies show that CUS alters the IIIb:IIIc ratio in favor of IIIb for both FGFR2 and FGFR3. These data suggest that stress controls the splice variant specific expression of FGFR2 and FGFR3 in a manner that can alter the pharmacological profile of these receptors and their preferential response to endogenous ligands. To our knowledge, this is the first report of splice-variant specific transcriptional control in the brain following stress.