Abstract: It is well documented that chronic stress can produce cognitive impairment, and that the hippocampus and prefrontal cortex play an important role in the process of learning and memory. The present study investigated the effects of chronic stress through examination of the modulation tone of FGF2 protein in hippocampus and prefrontal cortex. The fibroblast growth factor-2 (FGF2), a mitogen that is involved in brain development and regeneration, has been shown to facilitate neurogenesis and synaptic plasticity, as well as be involved in the mechanism of neurodegenerative disorders.
In the experiment, sixteen male Sprague-Dawley rats were randomly assigned into control group and stress group and the chronic unpredictable mild stress (CUMS) model was performed to construct chronic stress model of rats. The stress group received 35 days CUMS which were consisted of food deprivation, water deprivation, clip tail, feet shock, forced swimming in cold water, wet bedding, and disturbed light-dark cycle. Following the last stressor, stressed and non-stressed rats began training in the Morris Water Maze (MWM) and Y Maze to test the change of the ability of learning and memory about space clue fixed position and conditioned escape response. The changes of protein level of FGF2 in hippocampus and prefrontal cortex were observed by Western blot analysis and Immunohistochemistry analysis.
Compared with the rats of control group, the rats of stress group have obvious impairments in learning and memory. In the MWM, the rats exposed to stress had longer latencies to reach the hidden platform during training phase (p<0.01), and passed fewer times through the platform location (p<0.01). In the Y maze test, stressed rats needed more learning performances (p<0.05) and had less precision rate (p<0.05). The protein level of FGF2 was downregulated in hippocampus of rats (p<0.001), especially the dentate gyrus, CA1 neurons and CA3 pyramidal neurons. The same changes also happened in prefrontal cortex (p<0.001).
These findings demonstrate that chronic stress impairs learning and memory and downregulates FGF2 signal in the brain. These results indicate that FGF2 may be involved in the mechanism of cognitive lesions caused by chronic stress, and suggest that modulating the FGF2 signal may have therapeutic value in the treatment of neurodegenerative diseases.

Key words: FGF2, chronic stress, learning and memory, hippocampus, prefrontal cortex