Behavioral and fMRI analysis of functional recovery in Parkinsonian animals

帕金森病动物功能恢复的行为和功能磁共振成像分析

• 批准号: 6353143
• 负责人: ZHIMING ZHANG
• 金额: $ 16.9万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353143
• 关键词: Macaca mulatta; Parkinson's disease; behavior test; behavioral /social science research tag; bioimaging /biomedical imaging; brain mapping; disease /disorder model; dopamine; drug delivery systems; functional ability; functional magnetic resonance imaging; nervous system regeneration; neurochemistry; neurotrophic factors; psychomotor function

Trophic factor treatment offers a promising approach for ameliorating the injury and loss of dopamine neurons in Parkinson's disease. However, safe and efficacious methods for delivering trophic factors into the brain with minimal side effects need to be developed in order for this approach to be successful. In this project we test the concept of using programmable pumps for the controlled, site-specific delivery of trophic factors. Medtronic pumps are used to test the hypothesis that the chronic intracerebral infusion of GDNF stimulates functional recovery of the nigrostriatal dopamine system. Project 2 has two goals. The first is to quantify the changes in parkinsonian features accompanying chronic GDNF infusion into the lateral ventricle and the putamen. Bradykinesia, rigidity, posture, balance and tremor will be rated from standardized videotaped tests of movement functions. Coarse and fine motor movement times will be quantified using an automated Movement Assessment Panel. The second goal is to utilize functional magnetic resonance imaging (fMRI) to noninvasively follow functional changes in the nigrostriatal dopamine system in aminals showing behavioral recovery from chronic GDNF infusion. Amphetamine-induced stimulation of dopaminergic processes in the caudate nucleus, putamen and substantia nigra will be mapped by fMRI as animals undergo behavioral recovery.

营养因子治疗为改善帕金森病患者多巴胺神经元的损伤和丢失提供了一种很有前途的方法。然而，需要开发安全有效的方法，将营养因子输送到大脑中，并将副作用降至最低，才能使这种方法成功。在这个项目中，我们测试了使用可编程泵进行受控的、特定于现场的营养因子输送的概念。美敦力泵被用来检验这样的假设，即长期脑内注射GDNF刺激黑质纹状体多巴胺系统的功能恢复。项目2有两个目标。第一个是量化帕金森病特征的变化，伴随着向侧脑室和壳核长期注入GDNF。运动迟缓、僵硬、姿势、平衡和震颤将通过标准化的运动功能录像测试进行评级。粗略和精细的运动时间将使用自动运动评估小组进行量化。第二个目标是利用功能磁共振成像(FMRI)来无创性地跟踪显示慢性GDNF注射后行为恢复的氨基鼠黑质纹状体多巴胺系统的功能变化。随着动物行为的恢复，安非他明对尾状核、壳核和黑质中多巴胺能过程的刺激将通过功能磁共振成像进行定位。