抑郁症动物模型的建立以及甘丙肽的影响研究

发布时间：2018-06-23 18:17

本文选题：抑郁症 + 慢性非预见性应激　；参考：《华东师范大学》2008年硕士论文

【摘要】： 抑郁症作为当今世界十大心理疾病之一,越来越严重地危及到人们的身心健康和正常生活,并成为生物研究的前沿热门课题。本项目通过建立抑郁症动物模型,探讨神经肽甘丙肽(Galanin GAL)及其受体在抑郁症发生过程中的作用。 1、模型建立采用慢性非预见性应激(CUMS)和嗅球切除两种方法建立抑郁症大鼠模型,运用旷场实验(Open Field),水迷宫及血清皮质醇检测来评价模型,并通过高效液相(HPLC)检测其各个脑区单胺类神经递质5—羟色胺(5—HT)和去甲肾上腺素(NE)含量的变化。综合比较了慢性应激模型和嗅球切除模型的特点。结果显示,两种模型组大鼠的旷场实验得分明显降低,主动活动能力下降;空间学习记忆能力显著降低,血清皮质醇含量显著升高,慢性应激模型组脑内神经递质含量无明显变化,嗅球切除模型组脑内神经递质含量普遍下降,在特定脑区变化显著。 2、脑内GAL表达分析运用RT-PCR技术和荧光定量PCR对GAL及其受体进行定性和半定量检测。结果显示,慢性应激模型组GAL在中缝背核和海马均上调。甘丙肽受体1(GalR1)在下丘脑上调,在中缝背核及海马均下调。甘丙肽受体2(GalR2)在下丘脑、中缝背核及海马三个脑区均下调。与荧光定量PCR结果相吻合。嗅球切除模型组GAL在下丘脑及海马上调。GalR1在海马下调,在下丘脑及中缝背核上调。GalR2在下丘脑下调,在中缝背核及海马均上调。 3、脑室注射甘丙肽及其激动剂对抑郁症状的影响动物在建立慢性应激模型后,进行侧脑室埋管手术。侧脑室慢性注射GAL及GalR2选择性激动剂GAL2-11,观察对抑郁症状的影响。侧脑室注射GAL及GAL2-11后,旷场实验显示大鼠的主动活动能力显著增强,空间学习能力显著提高。结论慢性非预见性应激和嗅球切除分别模拟了抑郁症病人外源性和内源性的发病机制,经行为学和血清皮质醇评价均为成功的抑郁症模型。模型建立过程中GAL及其受体的表达在不同脑区出现不同的变化,而侧脑室慢性注射GAL及GalR2激动剂GAL2-11可减轻抑郁症状,提示GAL很有可能参与了抑郁症形成过程中神经元功能的调制。本项目为进一步探索在抑郁症发生发展过程中GAL及其受体与下丘脑、中缝背核和海马脑区神经元功能下降的相关性以及抑郁症发病的神经学机制及抗抑郁药的研制打下基础。
[Abstract]:Depression, as one of the ten psychological diseases in the world, is more and more seriously endangering people's physical and mental health and normal life, and has become a hot topic in biological research. By creating animal models of depression, To investigate the role of neuropeptide galanin gal and its receptors in the development of depression. 1. Chronic non-predictive stress (CUMS) and olfactory bulb resection were used to establish the rat model of depression. Open field test, water maze and serum cortisol detection were used to evaluate the model. The changes of monoamine neurotransmitters 5-HT and norepinephrine (NE) in various brain regions of the model were detected by high performance liquid chromatography (HPLC). The characteristics of chronic stress model and olfactory bulb resection model were compared. The results showed that the scores of open field test decreased significantly, the ability of active activity decreased, the ability of spatial learning and memory decreased significantly, and the content of serum cortisol increased significantly in both groups. The content of neurotransmitters in brain of chronic stress model group did not change obviously, but the content of neurotransmitter in olfactory bulb resection model group decreased generally. The expression of gal in brain was detected qualitatively and semi-quantitatively by RT-PCR and fluorescence quantitative PCR. The results showed that gal was up-regulated in dorsal raphe nucleus and hippocampus in chronic stress model group. Galanin receptor 1 (GalR1) was up-regulated in hypothalamus, down-regulated in dorsal raphe nucleus and hippocampus. GalR2 was down-regulated in the hypothalamus, dorsal raphe nucleus and hippocampus. The results were consistent with the results of fluorescence quantitative PCR. In olfactory bulb resection model group, gal was up-regulated in hypothalamus and hippocampus. GalR1 was down-regulated in hippocampus and down-regulated in hypothalamus and dorsal raphe nucleus. In the dorsal raphe nucleus and hippocampus. 3. The effect of intraventricular injection of glycine and its agonist on depressive symptoms in rats was performed after chronic stress model was established. The effects of gal and GalR2 selective agonist GAL2-11 on depression were observed. After injection of gal and GAL2-11 into the lateral ventricle, open field experiments showed that the active activity and spatial learning ability of the rats were significantly enhanced. Conclusion chronic non-predictive stress and olfactory bulb resection can simulate the exogenous and endogenous pathogenesis of depression respectively. Both behavioral and serum cortisol evaluation are successful models of depression. The expression of gal and its receptors varied in different brain regions during the establishment of the model. The chronic injection of gal and GalR2 agonist GAL2-11 into the lateral ventricle alleviated the depressive symptoms. It is suggested that gal may be involved in the modulation of neuronal function in the process of depression. This project provides a basis for further exploring the relationship between gal and its receptors and the decrease of neuron function in hypothalamus dorsal raphe nucleus and hippocampal area during the occurrence and development of depression as well as the neuromechanism of depression and the development of antidepressants.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R-332;R749.4

【参考文献】