题名青少期抑郁水平与创伤后应激障碍模型大鼠行为以及NPYY2R的相关研究
作者赵静
答辩日期2021-12
文献子类硕士
授予单位中国科学院心理研究所
授予地点中国科学院心理研究所
其他责任者郭建友
关键词神经肤受体 抑郁 创伤后应激障碍 认知能力 个体差异
学位名称理学硕士
其他题名Correlation of depression levels in adolescence with the behavior of rats in a model of post-traumatic stress disorder and the NPY Y2R
学位专业健康心理学
中文摘要Objectives: According to a recent epidemiological survey, 29.2% and 54.7% of adolescents who had PTSD or suffered from PTSD during their lifetime also had depression, ranking first in the co-morbidity rate of PTSD and other psychological disorders. At present, one of the views on the causes of co-morbidity, "the level of depression before stress is a risk factor for the emergence of PTSD symptoms after stress",has made some progress, but it is not yet supported by evidence from experimental animal studies. In addition, clinical studies have revealed individual differences in symptom phenotypes and developmental trajectories of the two co-morbidities. Currently, there is a lack of research on the individual differences between the two co-morbidities. NPY is known to be strongly associated with individual differences in PTSD and depression; however, whether NPY Y2R receptors are involved in regulating PTSD and depression co-morbidity is unclear. The aim of this study was to investigate the relationship between adolescent depression levels and the behavior of rats with PTSD models, NPY Y2R, and to provide evidence for the prediagnosis of adolescent PTSD and depressed individuals as well as for prognostic treatment. Methods: A single prolonged stress model in rats was used to induce PTSD in adolescent rats. A combination of meta-analysis, animal behavioural and Western Blot and qRT-PCR methods was used to explore the correlation of depression levels in adolescence with the behavior of rats in a model of post-traumatic stress disorder and the NPY Y2R. Results:Study 1 is a review meta-analysis, the first meta-analysis for the effect of single prolonged stress model on depression-like behavior in animals, extracting the results of five databases of existing experimental studies exploring single prolonged stress model and depression-like behavior in rodents, which found that single prolonged stress could well induce depression-like behavior in animals; the results of the heterogeneity test showed individual differences in depression-like behavior in animals induced by the single prolonged stress model, and it was determined that the depression-like behavior of animals in the single prolonged stress model was measured using the sucrose preference test. Study 2 distinguished the psychologically vulnerable group, the psychologically resilient group and the control group according to the pre-stress sucrose preference level, and observed the effects of PTSD modeling on depression-like behaviors, spatial cognitive ability and non-spatial cognitive ability in the three groups of animals, and found that (1)there were no significant differences in desperate behaviors (immobility time) in the forced swim test between the psychologically vulnerable and psychologically resilient groups during single prolonged stress. After single prolonged stress, there was no significant difference in the level of sucrose preference among the three groups of rats; compared with pre-stress, the sucrose preference values increased significantly in the control group and did not change significantly in the stress group. The three groups did not differ significantly in anxiety一like behavior in the elevated plus maze after stress. (2) There was no significant effect of adolescent single prolonged stress on the non-spatial cognitive ability of rats, and there was no significant difference in the novel object recognition index of the three groups, but in the spatial cognitive ability water maze test, the learning task of finding the survival platform for the 5th to 8th times, the time to find the escape platform was significantly longer in the psychologically vulnerable rats than in the control and the time spent in the target quadrant was significantly lower in the psychologically resilient group than in the control rats during the memory test phase. Study 3 used Western Blot and qRT-PCR to analyze the expression level of hippocampal NPY Y2R in adolescent rats, and found that single prolonged stress in adolescence was found to have a significant effect on protein expression rather than mRNA expression levels of NPY Y2R in the rat hippocampus, as shown by the protein expression level of hippocampal NPY Y2R in rats in the psychologically vulnerable group was significantly reduced, and further correlation analysis showed that changes in the time of staying in the escape platform of the water maze in rats were significantly and positively correlated with the hippocampal NPY Y2R protein expression. Conclusions:Based on the above results, the level of adolescent depression affects the spatial learning ability of rats in the psychologically vulnerable group and the spatial memory ability of rats in the psychologically resilient group after post-traumatic stress disorder modeling, which may be mediated by protein expression of NPY Y2R receptors in hippocampal region.
英文摘要目的:根据最近一项流行病学调查结果显示,曾经患有或终生患PTSD的青少年人群中有高达29.2%与54.7%同时患有抑郁症,排在PTSD与其他心理疾病共病率的首位,探讨二者高共病率的发生发展及其成因机制对临床早期干预和治疗具有重要意义。口前,关于二者共病成因的观点之一“应激前的抑郁水平是应激后的PTSD症状出现的危险因素”虽然取得了一定的进展,但是尚未获得动物实验研究证据的支持。此外,临床研究揭示两者共病在症状表型和发展轨迹上具有个体差异性。口前,对于两者共病的个体差异性研究还比较缺乏。己知NPY与创伤后应激障碍个体差异性和抑郁症的关系密切,然而,NPYY2R受体是否参与调节PTSD与抑郁症共病尚不清楚。本研究旨在探讨青少期抑郁水平与创伤后应激障碍模型大鼠行为、NPY Y2R的关系,为青少年PTSD和抑郁个体的预前诊断以及预后治疗提供证据。 方法:采用大鼠单次延长应激模型诱发青少期大鼠创伤后应激障碍,结合元分析、动物行为学和Western Blot, qRT-PCR方法,探讨了青少期抑郁水平与创伤后应激障碍模型大鼠行为以及海马区域NPY Y2R之间的关系。 结果:研究一是综述性元分析,首次针对单次延长应激模型对动物抑郁样行为的影响进行元分析,提取五个数据库己有探究单次延长应激模型与啮齿类动物抑郁样行为的实验研究结果,结果发现单次延长应激可以很好地诱导出动物的抑郁样行为;异质性检验结果显示单次延长应激模型引起的动物抑郁样行为具有个体差异性,确定使用糖水偏好测试测量单次延长应激模型动物的抑郁样行为。研究二根据应激前糖水偏好水平的高低区分出心理易感组、心理韧性组和控制组,观察创伤后应激障碍造模对三组动物的情绪行为、空间认知能力和非空间认知能力的影响,结果发现(1)单次延长应激过程中心理易感组和心理韧性组的强迫游泳测试中的绝望行为(不动时间)没有显著差异;创伤后应激障碍造模后,三组大鼠的糖水偏好水平无显著差异;与应激前相比,控制组糖水偏好值显著增加,应激组糖水偏好值没有显著改变;三组在应激后高架十字迷宫的焦虑样行为中没有显著差异。C2}青少期单次延长应激对大鼠非空间认知能力没有显著的影响,三组的新物体识别指数没有显著差异,但是在空间认知能力水迷宫测试中,第5到8次找到求生平台的学习任务中,心理易感性大鼠找到逃生平台的时间显著长于控制组,记忆测试阶段心理韧性组停留口标象限时间显著低于控制组大鼠。研究三采用Western Blot, qRT-PCR分析青少期大鼠海马NPY Y2R的表达水平,发现青少期单次延长应激对大鼠海马NPY Y2R的蛋白表达有显著影响而非mRNA表达水平,具体表现为心理易感组大鼠海马NPY Y2R的蛋白表达水平显著降低,进一步相关分析显示,青少期应激导致的大鼠水迷宫停留在逃生平台时间的变化与海马NPY Y2R蛋白表达呈显著正相关。 结论:根据以上结果得出结论,青少期抑郁水平影响创伤后应激障碍造模后心理易感组大鼠的空间学习能力和心理韧性组大鼠的空间记忆能力,这可能是由海马区域NPY Y2R受体的蛋白表达介导。
语种中文
内容类型学位论文
源URL[http://ir.psych.ac.cn/handle/311026/41346]  
专题心理研究所_健康与遗传心理学研究室
推荐引用方式
GB/T 7714
赵静. 青少期抑郁水平与创伤后应激障碍模型大鼠行为以及NPYY2R的相关研究[D]. 中国科学院心理研究所. 中国科学院心理研究所. 2021.
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