下丘腦NPY在慢性應激誘發(fā)抑郁中的作用
發(fā)布時間:2018-05-17 06:43
本文選題:神經(jīng)肽Y + 抑郁 ; 參考:《南昌大學》2013年碩士論文
【摘要】:抑郁癥是心境障礙(Mood disorder)的一種,以情緒低落、興趣缺乏、和快感缺失為核心癥狀,其發(fā)病與遺傳因素、神經(jīng)生化因素和心理社會因素有關。隨著社會競爭和生活壓力的增大,抑郁癥的發(fā)病率不斷升高。對抑郁癥的發(fā)病機制及防治方法的研究一直是神經(jīng)領域科學研究的熱點。 下丘腦-垂體-腎上腺(HPA)軸是維持機體正常功能狀態(tài)的一個重要調節(jié)系統(tǒng)。長期應激導致HPA軸的過度激活以及糖皮質激素(GC)分泌的增加,持續(xù)高水平的GC分泌進而導致機體一系列的病理效應,如抑郁癥、高血壓病、糖尿病、應激性潰瘍等。隨著對抑郁癥發(fā)生機制相關研究的逐步深入,對神經(jīng)肽Y(NPY)在應激反應和焦慮抑郁中所發(fā)揮的作用近年日益受到重視。但有關NPY通過調控HPA軸來影響抑郁癥發(fā)病的確切機制尚未得到闡明。 本研究通過建立慢性不可預見性應激(chronic unpredictable stress, CUS)大鼠抑郁模型,采用對大鼠下丘腦室旁核內(nèi)進行微量注射NPY,對大鼠體重變化進行測量,進行糖水偏愛和強迫游泳試驗等行為學測試,并結合檢測血清ACTH和CORT水平變化、下丘腦室旁核GR蛋白表達改變等方法來探討NPY在慢性應激性抑郁發(fā)生中的作用。 研究結果如下:1.與對照組大鼠相比,慢性不可預見性應激(CUS)組大鼠體重增長呈下降趨勢,表現(xiàn)出明顯的抑郁樣行為變化,血清ACTH和CORT水平升高,且下丘腦室旁核GR蛋白表達減少。2.單獨下丘腦室旁核微量注射NPY對大鼠的體重增長變化、行為變化、血清激素水平和GR蛋白表達沒有顯著影響。3. NPY+CUS組大鼠體重總體呈上升趨勢,下丘腦室旁核微量注射NPY后對CUS大鼠抑郁樣行為呈明顯改善作用,并降低大鼠血清ACTH和CORT水平,以及增加PVN區(qū)的GR蛋白表達。 綜上所述,,CUS可引起體重增長下降和抑郁樣行為表現(xiàn),減少PVN區(qū)GR蛋白表達。而下丘腦室旁核微量注射NPY可通過增加PVN區(qū)GR蛋白表達,降低ACTH、CORT激素水平來改善慢性應激引起的抑郁樣行為表現(xiàn)。所以,調控大腦特異性核團區(qū)特別是PVN區(qū)的NPY水平,可能是抑郁癥防治的一種新的思路。
[Abstract]:Depression is a kind of mood disorder mood disorder.It is characterized by depression, lack of interest, and lack of pleasure. The pathogenesis of depression is related to genetic factors, neurobiochemical factors and psycho-social factors. With the increase of social competition and life pressure, the incidence of depression is increasing. The research on the pathogenesis and prevention of depression has been a hot spot in the field of neuroscience. The hypothalamus-pituitary-adrenal gland (HPA) axis is an important regulatory system to maintain the normal function of the body. Long-term stress leads to excessive activation of HPA axis and increase of glucocorticoid secretion, which leads to a series of pathological effects, such as depression, hypertension, diabetes, stress ulcer and so on. With the deepening of the research on the mechanism of depression, the role of neuropeptide YG NPY in stress response and anxiety and depression has been paid more and more attention in recent years. However, the exact mechanism of NPY affecting depression by regulating the HPA axis has not been clarified. In this study, the depression model of chronic unpredictable stress, CUS) rats under chronic unpredictable stress was established, and the changes of body weight of rats were measured by microinjection of NPY into the paraventricular nucleus of hypothalamus. To explore the role of NPY in the development of chronic stress depression, behavioral tests such as sugar water preference and forced swimming test were carried out, and the changes of serum ACTH and CORT levels and the expression of gr protein in hypothalamic paraventricular nucleus were measured to explore the role of NPY in the development of chronic stress depression. The results are as follows: 1. Compared with the control group, the rats in the chronic unpredictable stress group showed a decreasing trend of weight gain, obvious depressive behavior, increased serum ACTH and CORT levels, and decreased expression of gr protein in hypothalamic paraventricular nucleus (PVN). Microinjection of NPY into paraventricular nucleus of hypothalamus had no significant effect on weight gain, behavior, serum hormone level and gr protein expression in rats. The weight of rats in NPY CUS group showed an upward trend, and the hypothalamic paraventricular nucleus microinjection of NPY could significantly improve the depressive behavior of CUS rats, decrease the levels of serum ACTH and CORT, and increase the expression of gr protein in PVN area. In conclusion, CUS could induce weight loss and depressive behavior, and decrease the expression of gr protein in PVN. Microinjection of NPY into the paraventricular nucleus of hypothalamus could improve the depressive behavior induced by chronic stress by increasing the expression of gr protein in PVN region and decreasing the level of ACTHCORT hormone. Therefore, regulating the level of NPY in the brain specific nuclei, especially in the PVN region, may be a new idea for the prevention and treatment of depression.
【學位授予單位】:南昌大學
【學位級別】:碩士
【學位授予年份】:2013
【分類號】:R749.4
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