Interactions between Classical Neurotransmitter Systems and Neuropeptide Systems in Experimental Animal Model of Parkinsonism

帕金森病实验动物模型中经典神经递质系统与神经肽系统的相互作用

基本信息

批准号：
61570387
负责人：
OGAWA Norio
金额：
$ 1.47万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

Interactions between classical neurotransmitter systems and neuropeptide systems were studied in experimantal animal model of parkinsonism. It was revealed that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, Weaver mice and 6-OHDA double (substantia nigra and lateral ventricle)-treated rats were suitable model for parkinsonism. In the rats with double administrations of 6-OHDA, the noradrenaline concentration strongly decreased in the almost all brain regions, indicating that this animal model is best model for advernced stage of parkinsonism. In the animal model, the concentration of D-2 dopamine receptor increased significantly but recovered to the normao level after administration of L-dopa. On the other hand, the concentration of the striatal muscarinic cholinergic receptor (MCR) decreased significantly but recovered to the normal level after administration of L-dopa. These findings indicated that the striatal MCR are strongly requlated by the nigrostriatal dopaminergic function. Substance P, cholecystokinin-octapeptide and somatostatin levels showed no change in any brain region of animal models. Interestingly, striatal somatostatin level showed a marked decrease in chronic phase of MPTP mice. Somatostatin receptor binding increased in the model animal, but did not recovered by administration of L-dopa. These data suggest that core biochemical dysfunctions in parkinsonism are changes in dopaminergic and cholinergic systems, and changes in neuropeptide systems are seconderily changes due to dopaminergic dysfunctions.Experimental animal model of parkinsonism is expected to be valuable in the studies on the biochemical pathophysiology of Parkinson's disease, the development of new drugs and studies on the therapeutic regiments to minimize the side effects.

在帕金森氏症的实验动物模型中研究了经典神经递质系统与神经肽系统之间的相互作用。据透露，1-甲基-4-苯基1,2,3,6-四氢吡啶（MPTP）处理的小鼠，织布剂小鼠和6-OHDA Double（黑质NIGRA和侧心）治疗的大鼠是适合帕克森主义的模型。在具有6-OHDA的双重施用的大鼠中，几乎所有大脑区域的去甲肾上腺素浓度都大大降低，这表明该动物模型是帕金森氏症的最佳模型。在动物模型中，D-2多巴胺受体的浓度显着增加，但在施用L-DOPA后恢复到Normao水平。另一方面，纹状体毒蕈碱胆碱能受体（MCR）的浓度显着降低，但在施用L-DOPA后恢复到正常水平。这些发现表明，纹状体MCR通过斑纹纹状体多巴胺能函数强烈重新加油。 PESTANCE P，胆囊基蛋白蛋白二摄氏肽和生长抑素水平在任何动物模型的任何大脑区域都没有变化。有趣的是，纹状体生长抑素水平在MPTP小鼠的慢性期显着降低。在模型动物中，生长抑素受体的结合增加，但没有通过L-DOPA的给药来恢复。这些数据表明，帕金森氏症的核心生化功能障碍是多巴胺能和胆碱能系统的变化，神经肽系统的变化是多巴胺能力功能障碍引起的逐渐变化的。帕金森主义的经验性动物模型在研究中有价值的研究在生物学疾病的研究中是有价值的。降低副作用的机制。