FGF-2 promotes new cell survival in hippocampus and decreases anxiety-like behavior: differential effects in animals with low novelty-seeking behavior

Society for Neuroscience. 2006.


Low Responder (LR) rats, characterized by decreased locomotor responsiveness to novelty, show higher rates of cell proliferation in the Hippocampal Dentate Gyrus (DG) relative to high responder (HR) rats, as measured by Ki-67 immunohistochemistry. However, when cell survival is measured 3 weeks after BrdU labeling the number of surviving cells does not differ between HR and LR animals. This suggests a lower rate of cell survival of newly born cells in LR animals and points to a difference in turnover rate or dynamics of neurogenesis between these phenotypic groups. Moreover, we have recently shown that HR animals have higher basal levels of FGF2 mRNA in the DG than LR, and that FGF-2 injections on postnatal day 1 can increase neuronal survival during the course of development. Therefore, we hypothesized that HR-LR differences in FGF2 expression could contribute to the observed differences in turnover rates of new cells in the DG. We asked whether chronic administration of FGF-2 in the adult rat can alter cell survival, and whether the effect is similar across the two behavioral phenotypes. Male Sprague-Dawley rats selectively bred for HR and LR phenotypic behavior were injected with BrdU for two days prior to being either administered FGF2 or vehicle for a period of 3 weeks. One day after the last injection, animals were tested in the elevated plus-maze (EPM) or perfused for BrdU immunohistochemistry. LR animals treated with FGF2 showed an increase in the number BrdU surviving cells compared to vehicle treated LR animals, whereas no change was observed in HR animals. Furthermore, LR rats treated with FGF2 showed reduce anxiety-like behavior by spending more time in the open arms of the EPM compared to controls. Interestingly, the anxiolytic response of FGF2 treatment was specific to LR animals, as no change was observed in HR animals. These results implicate FGF2 in modulating individual differences in the rate of cell survival which in turn may relate to differences in emotional response to novelty.