| Objective:It is well known that prolonged stress can influence the emotion and cognitive processes. Chronic psychological stress seems to facilitate increased sensitivity to mood disorders and neurodegenerative diseases. Hippocampus and prefrontal cortex play an important role in emotion regulation and information processing. Fibroblast growth factor system is involved in many physiological processes during early development and throughout adulthood of brain, including neuron proliferation, migration, differentiation, survival, and regeneration. The present study investigated the effects of chronic stress on emotion and cognition processes, as well as the modulation tone of FGF2,FGFR1 protein in hippocampus and prefrontal cortex following chronic unpredictable mild stress.Methods:16 male Sprague-Dawley rats were randomly divided into control group and stress group. The chronic unpredictable mild stress model was performed, including food deprivation, water deprivation, clip tail, feet shock, forced swimming in cold water, disturbed light-dark cycle, and wet bedding. The body weight of all rats was recorded throughtout the experiment process. Mood state was evaluated by saccharin preference test and open-field test. The changes of cognitive processing were tested through Morris water maze and Y maze. After the behavior tests, all rats were decapitated , and brains were rapidly removed. The changes of protein were observed by Western blotting analysis and Immunohistochemical analysis. At last, the correlation between the behavior indicators of emotion and cognition and the expression levels of FGF2-FGFR1 protein was analysed.Results:(1) Compared with the rats of control group, the rats of stress group have obvious impairments in emotion regulation and cognitive processing, especially the anxiety, ahedonia, locomotor, exploratory behavior, learning and memory. In the saccharin preference test, the stressed rats had less saccharin solution intake . But the total liquid intake did not differ among groups. In the open-field test, the chronic stress gave rise to longer residence time in the central area, shorter horizontal move distance, and smaller number of standing up-right. In the MWM, the rats exposed to stress had longer latencies to reach the hidden platform during training phase, and passed fewer times through the platform location. In the Y maze test, stressed rats needed more learning performances and had less precision rate.(2)Compared with the normal rats , the rats of stress group had obvious downregulates of protein expression. The protein level of FGF2 and FGFR1 was downregulated in hippocampus of rats, especially the dentate gyrus, CA1 neurons and CA3 pyramidal neurons. The same changes also happened in prefrontal cortex .(3)The results of correlation analysis indicated that, the expression level of FGF2 and FGFR1 protein in hippocampus and prefrontal cortex had correlation with behavior indicators of emotion and cognition. The significant correlation existed between ahedonia and the protein of FGF2 in CA1, FGFR1 in prefrontal cortex; locomotor and the protein of FGFR1 in CA3 and DG; exploratory behavior and protein FGFR1 in prefrontal cortex; learning ability and FGF2 protein in hippocampus, memory and FGF2 -FGFR1 protein of prefrontal cortex.Conclusion:These findings strongly suggest that chronic stress apparently impairs emotion regulation and cognitive processing, and downregulates the expression of FGF2 and FGFR1 protein in the hippocampus and prefrontal cortex. These results implicate that FGF2 and FGFR1 may be involved in the mechanism of mood disorders and cognitive lesions caused by chronic stress, and suggest that modulating the FGF2 and FGFR1 signal may have therapeutic value in the treatment of mood disorders and neurodegenerative diseases. |
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