下丘脑NPY在慢性应激诱发抑郁中的作用

发布时间：2018-05-17 06:43

本文选题：神经肽Y + 抑郁　；参考：《南昌大学》2013年硕士论文

【摘要】：抑郁症是心境障碍（Mood disorder）的一种，以情绪低落、兴趣缺乏、和快感缺失为核心症状，其发病与遗传因素、神经生化因素和心理社会因素有关。随着社会竞争和生活压力的增大，抑郁症的发病率不断升高。对抑郁症的发病机制及防治方法的研究一直是神经领域科学研究的热点。下丘脑-垂体-肾上腺（HPA）轴是维持机体正常功能状态的一个重要调节系统。长期应激导致HPA轴的过度激活以及糖皮质激素（GC）分泌的增加，持续高水平的GC分泌进而导致机体一系列的病理效应，如抑郁症、高血压病、糖尿病、应激性溃疡等。随着对抑郁症发生机制相关研究的逐步深入，对神经肽Y（NPY）在应激反应和焦虑抑郁中所发挥的作用近年日益受到重视。但有关NPY通过调控HPA轴来影响抑郁症发病的确切机制尚未得到阐明。本研究通过建立慢性不可预见性应激（chronic unpredictable stress, CUS）大鼠抑郁模型，采用对大鼠下丘脑室旁核内进行微量注射NPY，对大鼠体重变化进行测量，进行糖水偏爱和强迫游泳试验等行为学测试，并结合检测血清ACTH和CORT水平变化、下丘脑室旁核GR蛋白表达改变等方法来探讨NPY在慢性应激性抑郁发生中的作用。研究结果如下：1.与对照组大鼠相比，慢性不可预见性应激（CUS）组大鼠体重增长呈下降趋势，表现出明显的抑郁样行为变化，血清ACTH和CORT水平升高，且下丘脑室旁核GR蛋白表达减少。2.单独下丘脑室旁核微量注射NPY对大鼠的体重增长变化、行为变化、血清激素水平和GR蛋白表达没有显著影响。3. NPY+CUS组大鼠体重总体呈上升趋势，下丘脑室旁核微量注射NPY后对CUS大鼠抑郁样行为呈明显改善作用，并降低大鼠血清ACTH和CORT水平，以及增加PVN区的GR蛋白表达。综上所述，，CUS可引起体重增长下降和抑郁样行为表现，减少PVN区GR蛋白表达。而下丘脑室旁核微量注射NPY可通过增加PVN区GR蛋白表达，降低ACTH、CORT激素水平来改善慢性应激引起的抑郁样行为表现。所以，调控大脑特异性核团区特别是PVN区的NPY水平，可能是抑郁症防治的一种新的思路。
[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.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.4

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