Effects of early postnatal FGF-2 administration on neurogenesis, emotionality and gene expression in rats.

C.A. Turner; C. Isgor; S.J. Evans; C.R. Neal; H. Akil; S.J. Watson
Society for Neuroscience 34th Annual Meeting. 2004.


Recent microarray findings in human postmortem tissue have pointed to significant changes in the FGF system in severe depression (Evans et al., under review). These results have suggested a potential role of the FGF system in the control of mood and emotions. Here, we test the hypothesis that neonatal administration of FGF-2 may alter emotionality, as well as neurogenesis and gene expression in the hippocampus. Sprague-Dawley rats were injected with either vehicle or FGF-2 (20ng/g, s.c.) on postnatal day 2 (PD2). Three weeks after injection we evaluated dentate gyrus volume and cell counts by Nissl staining. We also assessed neurogenesis by BrdU and Ki-67 immunohistochemistry at the 23 day time point. As adults, we tested locomotor activity, anxiety behavior and learning and memory. The animals were sacrificed, and the brains collected for in situ hybridization (FGF markers, stress markers). Results to date have shown the following: FGF-2 injected rats exhibited a 10.5% increase in dentate gyrus volume. When tested as adults, a single neonatal exposure of FGF-2 significantly increased locomotor activity over controls in a novel environment. Increased activity in response to novelty has been associated with a host of other measures including decreased anxiety-like behavior. Furthermore, adult rats that received FGF-2 as neonates also performed significantly better than controls in the Morris water maze. These results indicate long-term alterations in hippocampal volume, emotional reactivity and learning and memory after a single postnatal FGF-2 injection. Whether or not these changes also correlate with alterations in neurogenesis and/or gene expression is currently being determined. These findings provide evidence supporting the hypothesis that the FGF system may play a role in mood disorders.