Long-term changes in hippocampal gene expression after early postnatal FGF2 administration

C.A. Turner; E. Gula; S.J. Evans; H. Akil; S.J. Watson
Society for Neuroscience annual meeting. 2005.


Previously, we have shown the FGF system to be dysregulated in individuals with major depressive disorder (MDD). We have also demonstrated that rats injected with FGF2 as neonates perform better on a learning and memory task and exhibit alterations in hippocampal morphology as adults. In the current study, we tested the hypothesis that an early postnatal injection of FGF2 may have long-term effects on hippocampal gene expression. To this end, Sprague-Dawley rats were injected with either vehicle or FGF2 (20ng/g, s.c.) the day after birth and sacrificed after Morris water maze testing as adults. We assessed changes in gene expression using both a candidate approach and a gene discovery approach with laser-capture microdissection of the dentate gyrus followed by microarray analyses. Results to date have found several genes associated with neural plasticity to be altered. We are currently confirming these results by RT-PCR and in situ hybridization. These results indicate long-term alterations in hippocampal gene expression associated with early FGF2 administration that also correlated with improved performance on a learning and memory task. These findings suggest that alterations in the FGF system be responsible for some of the cognitive deficits seen in individuals with MDD. Supported By: The Pritzker Neuropsychiatric Disorder Research Consortium Fund and NIMH Program Project Grant #MH42251-01.