The Study Of The Damage And Anti-Damage In Central Nerve System Under Different Stress Period

Stress is a responsive state including neurological, endocrinological and immunelogical responses when the body is threatened by adverse change in environment. Moderate stress can improve adaptability of the body and maintain its homeostasis, but chronic or severe stress could damage organism and induce multi-system disorders such as depression, learning and memory disorder, and dementia. Furthermore, stress can accelerate aging and hypoimmunity.Activated hypothalamus-pituitary-adrenal (HPA) axis and over-secretion of glucocorticoid are the key characters of stress response. The activation of HPA is an important adaptive response, and the secretion of glucocorticoid benefits to mobilize energy and keeps homeostasis, but the chronic glucocorticoid-emia is harmful to central nervous system. There are some regions in CNS that relate closely with stress, such as hippocampus, amygdala, hypothalamus, prefrontal cortex and striatum. Chronic stress or exogenous cortisol leads to cell denaturation and loss, dendrite atrophy in hippocampus and prefrontal cortex, and decreases monoamine neurotransmitter in striatum.Brain derived neurotrophic factor (BDNF) is one of the members of NTs family. It distributes widely in cerebral cortex, hippocampus, basal forebrain, stratum, septum, hypothalamus and cerebellum. BDNF can not only promote survival and differentiation, but also offer nutrition and protection of neurons. The evidence from animal study indicated that BDNF was closely related with stress. Chronic stress makes the expression level of BDNF decrease obviously in CA3 of rat hippocampus and prefrontal cortex. The levels of BDNF in cortex and stratum are also down-regulated significantly in brain ischemical reperfusion injury and Parkinson's disease.Studies showed that estrogen involved in electrophysiology, neurotrophy and metabolism. Estrogen can regulate expression of BDNF and receptor of BDNF, meanwhile, BDNF regulates estrogen receptor in different cell population. That means estrogen provides its protection for neurons by "co-regulation" with BDNF. There is dysfunction of Hippocampus-pituitary-gonad (HPG) axis in chronic stress. The lower level of estrogen and expression of BDNF make them lose their protection ability in chronic stress. Researchers thought that increasing the level of estrogen and enhancing BDNF expression during stress by exogenous intervention may counteract stress. The evidence from clinical research had proved that estrogen replacement therapy (ERT) can improve mental function after parturition in women with mental disorder and the cognition after menopause, ERT also had therapeutic action on Alzheimer's disease (AD) and Ischemic Brain injury in clinical practise. But, application of estrogen is restricted because longtime intaking of estrogen can increase vulnerability to breast cancer, uterine tumor or tumor of the ovary. The traditional Chinese medicine "QIANJINFUBAO" (QJFB) is the preparation of pure herb, which is based on the principle of supplementing the renal function and regulating the liver function, strengthening the vigor and supplying for the blood. The clinical observation has proved that it had therapeutic effect for women endocrine functional disorders.Using the chronic unpredictable mild stress model, the study observed the behavior, serum estrogen, morphologic changes in sub regions of brain (hippocampus, cortex, striatum), and BDNF expression to investigate: (1) The changes of behavior, serum level of estradiol and the dynamic expression of BDNF during chronic stress period. (2) The protection of QJFB to counteract chronic stress injury. The results as followed: 1. Compared with the control group, the stress group rats spent more time in the central square, had significant less square crossing numbers, vertical movement scores and grooming numbers on 14^th day and 21^st day of stress.2. Compared with the control group, there were less sucrose solution and sucrose preference on 2^nd day, 14^th day and 21^st day of stress.3. Compared with the control group, there were morphology changes such as cell swell and hypochromatic in sub regions of brain on 7^th day of stress; there were cell shrunk and intercellular spaces increased on 14^th day of stress; there were significant neurons degenerative atrophy and nucleolus condensed and ruptured on 21^st day of stress. The neurons of striatum and frontal cortex were injured, including decreased cell number, cell degeneration and apoptosis.4. Compared with control group, there were significant reduction of BDNF expression in sub regions of brain on 7^th, 14^th, 21^st day of stress.5. Compared with control group, there were significant lower level of E₂ on 2^nd, 14^th, 21^st day of stress.6. There were significant high level of E₂, significant improved scores in "OF test" and significant increased sucrose consumption and sucrose preference, significant improved the morphology and BDNF expression in sub regions of brain in QJFB group.Conclusion:1. Chronic unpredictable mild stress could induced inhibition of behavior, these changes appeared from 7^th day to 14^th day of stress and continual to 21^st day.2. Chronic unpredictable mild stress could decrease the sucrose consumption and the level of E₂, there was an obviously persistence decline on 14^th and 21^st day of stress.3. Chronic unpredictable mild stress could cause the changes of morphology and the decrease of BDNF expression in different regions of brain, these changes appeared from 2^nd day to 7^th day of stress and continual to 21^st day. These stable changes of axoneure morphology and BDNF expression were earlier than those of behavior and serum estrogen. 2. QJFB could increase the independent behavior and response to reward in chronic stress rats; elevate the serum estrogen and BDNF expression in sub regions of brain; improve the axoneure morphology significantly. All of these suggest that during chronic stress, QJFB can maintain estrogen secretion and have protection against stress damage.