Study Of The Establishment Of The Depression Model And Galanin's Effect

As one of the top ten mental illnesses in today' s world, depression is more and more endangering people' s normal lives. Therefore, it becomes a hot front porch issue in the bioresearch. In this thesis, based on the establishment of the depression model, we try to find the effect of GAL and its receptors in the depression process.We use both chronic unpredictable mild stress (CUMS) and olfactory bulbectomy (OB) methods to build the depression models, and reply on the Open Field Test and Morris Water Maze Test and blood cortisol level to evaluate those models. Moreover, the HPLC was used to detect the contents of 5-HT and NE in four encephalic regions, including caudate, hypothalamus, raphe nucleus and hippocampus. Open Field results showed that the score of the model group evidently lower than that of control group, the initiative locomotion activity decreased deeply. The ability of learning and memory decrease evidently either. And the content of the cortisol in the blood serum increased deeply compared to the control group. The HPLC results showed that the contents of the monoamine transmitters in the brain have no obvious changes between the CUMS model group and the control group, but in the OB model group, the contents of the transmitters decrease deeply. We used the RT-PCR technology and FQ-PCR to test the expression of Galanin (GAL) and its receptors in three encephalic regions. In the CUMS model group, the expression of GAL increased in both raphe nucleus and hippocampus. The expression of Galanin receptor1 (Ga1R1) increased in hypothalamus but decreased in both raphe nucleus and hippocampus. In the three encephalic regions, the expression of Galanin receptor2 (Ga1R2) decreases also. The FQ-PCR test showed the same results. In the OB model group, the expression of GAL in raphe nucleus had no obvious change, but increased in both hypothalamus and hippocampus. The expression of Ga1R1 decreased in hippocampus but increased in both raphe nucleus and hypothalamus. In the three encephalic regions, GalR2 had high expression.Finally, we used the lateral ventricle (LV) injection technology to test the behavior change of the model animals. After we injected GAL and GalR2 antagonist GAL2-11 into the LV of the model animals, the results of Open Field test showed the locomotion activity increased obviously, and the Water Maze Test showed the same change and increased the learning ability evidently.The two depression model establishment methods can separately simulate endogenous and exogenous mechanism of depression disease. The Open Field Test, Water Maze Test and cortisol test showed both models are successful. The changes of the expression of GAL and its receptors in different encephalic regions suggest it probably take part in modulating neural functions during the depression process. The LV injection of GAL and GAL2-11 abateed the depression symptoms, this result support the above suppose. This thesis is aimed at learning the relationship between expression of GAL and the function of neurons in hippocampus and dorsal raphe nucleus. It is important for further study of pathology and physiology of depression and is valuable for searching the antidepressant new compounds.