Recent microarray studies have revealed dysregulation of multiple genes related to the Fibroblast Growth Factor (FGF) family in several brain regions of subjects with a history of major depression, including decreased FGF-2 gene expression in the hippocampus. In the adult human, depression has been linked to reduced hippocampal volume, which may be associated with decreased neurogenesis. In turn the behavioral consequences of depression have been attributed in part to deficits in hippocampal neurogenesis. As genetic background has shown great influence on vulnerability or protection to this or other psychiatric diseases, it is evident that environmental factors pose a great impact on susceptibility for psychiatric illness. While chronic stress leads to increase anxiety and reduced levels of neurogenesis, environmental complexity has been shown to have the opposite effects. This project will investigate the potential role of FGF-2 on experience-dependent neurogenesis and emotional behavior in the rat. We hypothesize that FGF-2 plays a role in reducing anxiety-like behavior by maintaining enhanced levels of neurogenesis in the hippocampus. The Environmental Complexity (EC) model will be used to examine the effects of experience on FGF-2 expression in the adult rat hippocampus. FGF-2 will be administered to determine whether it prevents anxiety and increases neurogenesis in the adult rat, similar to EC. Finally, FGF receptor antagonists will be administered to determine whether the effects of EC on neurogenesis and anxiety are dependent upon FGF- 2 activity in the hippocampus. This work should lead to new discoveries of the molecular and structural mechanisms of how experience influences emotionality, which could help provide novel therapeutic strategies for psychiatric illness. ? ? ?
| Turner, Cortney A; Clinton, Sarah M; Thompson, Robert C et al. (2011) Fibroblast growth factor-2 (FGF2) augmentation early in life alters hippocampal development and rescues the anxiety phenotype in vulnerable animals. Proc Natl Acad Sci U S A 108:8021-5 |
| García-Fuster, M J; Perez, J A; Clinton, S M et al. (2010) Impact of cocaine on adult hippocampal neurogenesis in an animal model of differential propensity to drug abuse. Eur J Neurosci 31:79-89 |
| Perez, Javier A; Clinton, Sarah M; Turner, Cortney A et al. (2009) A new role for FGF2 as an endogenous inhibitor of anxiety. J Neurosci 29:6379-87 |
