乙酰胆碱激动剂对大鼠拟精神分裂症认知功能障碍的影响
发布时间：2018-07-31 13:41
【摘要】：精神分裂症是一种严重而复杂的精神疾病,认知障碍是其核心症状之一。己知乙酰胆碱系统是参与认知调节的中枢神经递质系统之一,且与目前公认的与精神分裂症关系密切的多巴胺系统有一定的相互作用。本研究通过青春期MK-801注射和青春期社会隔离两种建模方式,采用Morris水迷宫和前脉冲抑制两种行为检测方法,观察了乙酰胆碱激动剂加兰他敏对大鼠拟精神分裂症认知功能障碍的影响,并进一步探讨了其与中枢多巴胺神经递质系统的相互作用。 研究结果发现,青春期MK-801注射及社会隔离均能诱导成年大鼠前脉冲抑制的缺失,并显著降低了前额叶多巴胺D2受体的蛋白含量,但不影响青春期大鼠的前脉冲抑制。乙酰胆碱激动剂加兰他敏可以逆转上述拟精神分裂症动物模型的前脉冲抑制缺失,以及前额叶多巴胺D2受体蛋白含量的异常降低。 以上研究结果表明,通过对青春期动物进行MK-801注射和社会隔离,可以成功建立拟精神分裂症前脉冲抑制的动物模型,从而为进一步研究精神分裂症的神经机制奠定了基础。加兰他敏对前脉冲抑制缺失的逆转证实了乙酰胆碱激动剂对于精神分裂症认知障碍的治疗效果,为精神分裂症认知障碍神经机制研究以及相关新药的研发提供了基础。此外,加兰他敏对前额叶多巴胺D2受体蛋白含量异常降低的逆转以及这种逆转与前脉冲抑制逆转的一致性表明,乙酰胆碱激动剂对于前脉冲抑制的影响与前额叶多巴胺D2受体相关,二者之间的相互作用为进一步研究精神分裂症的发病机制提供了实验依据。
[Abstract]:Schizophrenia is a serious and complex mental disease, cognitive impairment is one of its core symptoms. Acetylcholine system is known to be one of the central neurotransmitter systems involved in cognitive regulation and has a certain interaction with the current recognized dopamine system which is closely related to schizophrenia. In this study, two modeling methods, MK-801 injection and social isolation, were used to detect the behavior of Morris water maze and pre-pulse suppression. The effects of acetylcholine agonist galantamine on cognitive dysfunction in rats with schizophrenia were observed and its interaction with central dopamine neurotransmitter system was further investigated. The results showed that MK-801 injection and social isolation could induce the absence of prepulse inhibition in adult rats, and significantly decreased the protein content of dopamine D2 receptor in prefrontal lobe, but had no effect on prepulse inhibition in adolescent rats. The acetylcholine agonist galantamine can reverse the prepulse inhibition deletion and the abnormal decrease of dopamine D2 receptor protein content in the prefrontal lobe of the above schizophrenic animal model. These results suggest that the animal model of prepulse suppression of schizophrenia can be successfully established by MK-801 injection and social isolation in adolescent animals, thus laying a foundation for further study of the neuromechanism of schizophrenia. The reversal of prepulse inhibition by galantamine confirms the efficacy of acetylcholine agonists in the treatment of cognitive disorders in schizophrenia and provides a basis for the study of the neuromechanism of cognitive disorders in schizophrenia and the development of related new drugs. In addition, galantamine reversed the abnormal decrease in dopamine D2 receptor protein content in prefrontal lobe and the consistency of this reversal with that of prepulse suppression. The effect of acetylcholine agonist on prepulse inhibition is related to dopamine D2 receptor in prefrontal lobe. The interaction between them provides experimental evidence for further study of the pathogenesis of schizophrenia.
【学位授予单位】：北京大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3;R96
[Abstract]:Schizophrenia is a serious and complex mental disease, cognitive impairment is one of its core symptoms. Acetylcholine system is known to be one of the central neurotransmitter systems involved in cognitive regulation and has a certain interaction with the current recognized dopamine system which is closely related to schizophrenia. In this study, two modeling methods, MK-801 injection and social isolation, were used to detect the behavior of Morris water maze and pre-pulse suppression. The effects of acetylcholine agonist galantamine on cognitive dysfunction in rats with schizophrenia were observed and its interaction with central dopamine neurotransmitter system was further investigated. The results showed that MK-801 injection and social isolation could induce the absence of prepulse inhibition in adult rats, and significantly decreased the protein content of dopamine D2 receptor in prefrontal lobe, but had no effect on prepulse inhibition in adolescent rats. The acetylcholine agonist galantamine can reverse the prepulse inhibition deletion and the abnormal decrease of dopamine D2 receptor protein content in the prefrontal lobe of the above schizophrenic animal model. These results suggest that the animal model of prepulse suppression of schizophrenia can be successfully established by MK-801 injection and social isolation in adolescent animals, thus laying a foundation for further study of the neuromechanism of schizophrenia. The reversal of prepulse inhibition by galantamine confirms the efficacy of acetylcholine agonists in the treatment of cognitive disorders in schizophrenia and provides a basis for the study of the neuromechanism of cognitive disorders in schizophrenia and the development of related new drugs. In addition, galantamine reversed the abnormal decrease in dopamine D2 receptor protein content in prefrontal lobe and the consistency of this reversal with that of prepulse suppression. The effect of acetylcholine agonist on prepulse inhibition is related to dopamine D2 receptor in prefrontal lobe. The interaction between them provides experimental evidence for further study of the pathogenesis of schizophrenia.
【学位授予单位】：北京大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3;R96
【参考文献】
相关期刊论文 前5条
1 金f，
本文编号：2155756
本文链接：https://www.wllwen.com/yixuelunwen/jsb/2155756.html
最近更新
教材专著
