Chronic Stress Depression Transforming Growth Factor And Its Relationship With Selenium Protein P Of -β1

Depression is a common affective disorder with high levels of morbidity, mortality and relapse rate. Chronic stress is a key factor of depression. In modern society, with the accelerating pace of life, people have to face more and more pressure from all aspects of life, which makes the incidence of depression rise year by year, so it brings great burden for people’s life and the development of national economy. According to the prediction of the World Health Organization, depression will become the foremost contributor to the worldwide burden of disease by2030.Study of depression pathomechanism, mainly from the neurotransmitter and receptor disorders and neuroplasticity et al. In recent years the neuroimmune in depression arouses more people’s attention. Transforming Growth Factor-beta1(TGF-β1) plays an important role in the inflammation, immune response and tissue injury, but also acts an a neurotrophic factor that protect neurons through several aspects. Studies suggested that TGF-β1abnormally expressed in depression. Selenoprotein P (SelP) plays an important role in the transportation and homeostasis of selenium (Se), and it’s also important for maintaining the normal function of brain. The genetic deletion of selenoprotein P in mice can result in severe neurological dysfunction and altered hippocampus synaptic function, which will lead to the disrupted spatial learning and motor coordination defect. Overproduced nitric oxide (NO) leads to neurological dysfunction and depression. iNOS antagonists has antidepressant effects. There are studies indicating that TGF-β1inhibits the expression of selenoprotein P and it reduce the production of NO by suppressing the expression of inducible nitric oxide synthase. These data suggust that there is relationship between TGF-β1. SelP, NO and depression. The change of hippocampal structure and function is closely related to the occurence of depression, however. it is still unclear about the chang, function and relationship of TGF-(31, SelP and NO in hippocampus in stress-induced depression.The present study tried to investigate the role of TGF-(31and its relationship with SelP and NO in stress-induced depression. Therefore we established the chronic unpredictable mild stress (CUMS) model in Sprague-Dawley. intra-hippocampal microinjection of recombined TGF-β1and LY-364947. the inhibitor of TGF-beta type I receptor kinase. The behavioral test was conducted by weight measurement, sucrose consumption, open-field test, and the tail suspension test. Then the expression level of selenoprotein P and TGF-β1was measured by immunohistochemistry, western blot and ELISA. NO was detected by Nitrate reduction kit.The data showed that compared with CON/SAL group, CUMS rats showed significant depression-like behaviors, lower expression of selenoprotein P and higher content of TGF-β1in the hippocampus. Microinjection of recombined TGF-β1didn’t result in animal depressive-like behaviors; however, intrahippocampal injection of recombined TGF-(31can effectively improved the depressive-like behaviors induced by CUMS. TGF-β1inhibited the expression of selenoprotein P. Interestingly, microinjection of LY-364947, the inhibitor of TGF-beta type I receptor kinase into hippocampus also showed anti-depression effect and the expression of selenoprotein P was higher compared with CUMS/SAL group. There was no significant change on the content of NO between groups with different treament.These results suggest that selenoprotein P and TGF-β1in the hippocampus are involved in chronic stress. Selenoprotein P may play a role in the protection of hippocampus. It may be involved in the occurrence of depression that TGF-β1inhibits the expression of selenoprotein P via TGF-beta type I receptor. TGF-beta1antidepressant effects may be via other ways without the TGF-beta type I receptor. Maybe it’s not the key to the function of selenoprotein P and TGF-β1to reduce the content of NO.