外侧缰核在帕金森大鼠抑郁行为中的作用及其机制研究

发布时间：2018-03-09 19:17

本文选题：外侧缰核　切入点：6-OHDA化学损毁模型　出处：《吉林大学》2014年博士论文　论文类型：学位论文

【摘要】：帕金森病（Parkinson’s disease，PD)是老年人常见的中枢神经系统退行性疾病，其运动障碍已为人们广泛关注。然而，40-50%的帕金森病人伴有精神情感障碍,严重降低PD患者生活质量，增加患者死亡率。大量的研究表明，PD的情感障碍不仅与黑质多巴胺系统受损有关，而且也有中枢5-羟色胺（5-hydroxytryptamine，5-HT）系统的功能异常，可能是中脑多巴胺和5-HT两大系统互相影响，共同作用的结果。许多研究表明，外侧缰核（Laterl habenular nucleu，LHb）与中脑多巴胺系统、中缝核五羟色胺系统间有密切解剖及功能联系，LHb不仅控制中脑多巴胺系统、中缝核五羟色胺系统的活动，并且也接受它们的传入信息，因而LHb可能是搭建两大系统信息传递的关键部位，参与PD大鼠情感障碍的发生。本研究首先通过6-OHDA化学损毁黑质多巴胺能神经元制备帕金森病大鼠模型，，并结合行为实验观察筛选伴有抑郁样行为的大鼠，随后从神经电生理、神经生化、行为学、放射性核素测定等多种角度，证明LHb在PD大鼠所致抑郁样行为中的作用和可能机制。本实验结果显示：系统应用多巴胺能激动剂可明显抑制外侧缰核神经元自发放电活动；帕金森病伴有抑郁行为的大鼠，LHb细胞色素氧化酶活性及葡萄糖代谢率均明显增加；电损毁LHb后可以明显改善PD大鼠的抑郁样行为；PD伴有抑郁样行为大鼠中缝核内五羟色胺含量降低，LHb损毁后可提高其中缝核内五羟色胺水平。结果表明，多巴胺可抑制LHb神经元活动，PD大鼠多巴胺功能低下导致LHb神经元活动增高可能与PD大鼠伴有的抑郁样行为有关，因此，损毁LHb能明显改善帕金森大鼠的抑郁样行为，其机制是通过提高中缝核五羟色胺水平来实现。本实验临床应用外科手术治疗PD情感障碍提供了一个新靶点。
[Abstract]:Parkinson's disease (PD) is a common degenerative disease of central nervous system (CNS) in the elderly, and its motor disorder has been paid more attention to. However, 40 to 50% of PD patients are associated with mental and emotional disorders, which seriously reduce the quality of life of PD patients and increase the mortality rate of PD patients. A large number of studies have shown that the affective disorder of PD is not only related to the damage of the substantia nigra dopamine system, but also to the dysfunction of the central 5-hydroxytryptamine5-HT system, which may be related to the interaction between the dopamine and 5-HT systems in the midbrain. Many studies have shown that Laterl habenular habenular LHb has a close anatomic and functional relationship with the midbrain dopamine system and the raphe nucleus serotonin system. LHb not only controls the activity of the midbrain dopamine system, but also the raphe nucleus system. LHb may be the key site of information transmission between two systems and participate in the occurrence of affective disorder in PD rats. In this study, the dopaminergic neurons of substantia nigra were chemically damaged by 6-OHDA to establish a rat model of Parkinson's disease, and the rats with depression-like behavior were selected by behavioral experiment, and then the neuroelectrophysiology, neurobiochemistry and behavior were studied. Radionuclide assay demonstrated the role and possible mechanism of LHb in depressive behavior in PD rats. The results showed that dopaminergic agonists could significantly inhibit the spontaneous discharges of neurons in the lateral habenular nucleus and the activity of LHb cytochrome oxidase and the rate of glucose metabolism were significantly increased in rats with Parkinson's disease and depressive behavior. After electrical lesion of LHb, the depressive behavior of PD rats was significantly improved. The content of serotonin in the raphe nucleus of PD rats decreased after the lesion of LHb. The results showed that the level of serotonin in the raphe nucleus of PD rats was increased after the lesion. Dopamine can inhibit the activity of LHb neurons. The increased activity of LHb neurons in PD rats may be related to the depressive behavior associated with LHb in PD rats. Therefore, damage of LHb can obviously improve the depressive behavior of PD rats. The mechanism is to increase the serotonin level of raphe nucleus. This experiment provides a new target for the surgical treatment of PD affective disorder.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R742.5

【共引文献】