BRAIN TISSUE TRANSPLANTATION: FUNCTIONAL ACTIVITY

脑组织移植：功能活动

• 批准号: 3404228
• 负责人: JILL B. BECKER
• 金额: $ 3.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404228
• 关键词: Parkinson's disease; adrenal medulla; brain metabolism; disease /disorder model; dopamine; embryo /fetus; experimental brain lesion; model design /development; nervous system transplantation; neurochemistry; neuropharmacology; neurotransmitter metabolism; substantia nigra

Depletion of brain dopamine (DA) in rats produces a syndrome of aphagia, adipsia, bradykinesia, and profound sensorimotor neglect. This bradykinesia and sensorimotor neglect is not due to a primary sensory or motor deficit, but has been characterized as a deficit in sensory-motor integration. These symptoms are very similar to those seen in Parkinson's Disease, which is thought to be due to a loss of DA-containing neurons in the substantia nigra. Although rats with bilateral DA depletion have provided many insights into the function of brain DA neurons, they are difficult to maintain, requiring extensive post-operative care. However, rats with unilateral nigrostriatal DA depletion have provided a very useful animal model of Parkinson's Disease. These animals neglect stimuli presented to the contralateral body surface or space, and when treated with DA-mimetic drugs display a highly quantifiable behavioral asymmetry known as rotational (circling) behavior. Recently, it has been shown that grafts of fetal substantia nigra or adrenal medulla tissue placed in or near the denervated striatum can at least partially reverse these behavioral asymmetries. The evidence available to date suggests that these grafts alleviate the symptoms of DA depletion by releasing catecholamines, but this hypothesis has never been directly tested. In this application we propose a series of experiments to do so. In the first series of experiments we propose to develop a push-pull perfusion technique to measure the efflux of catecholamine metabolites into the lateral ventricle as an index of catecholamine release. Next, we will compare the ability of fetal substantia nigra, adrenal medulla or fetal tectal tissue grafts placed into the lateral ventricle to release catecholamines and/or catecholamine metabolites into the lateral ventricle, over time following the transplant. Thirdly, we will use a series of pharmacological manipulations to determine: (1) if there is any relation between the ability of catecholamine-rich tissue grafts to release catecholamines and their ability to attenuate the rotational behavior imbalance produced by unilateral DA depletion; and (2) whether any of the normal mechanisms governing catecholamine release are operative in tissue grafts.

大鼠脑多巴胺（DA）的消耗产生了一种失语症， 缺乏视觉、运动迟缓和深度感觉运动忽视。 这 运动迟缓和感觉运动忽视不是由于初级感觉或 运动缺陷，但被描述为感觉运动缺陷 一体化 这些症状与帕金森氏症非常相似 疾病，这被认为是由于失去了DA-含有神经元， 黑质 尽管双侧DA耗竭的大鼠 提供了许多关于大脑DA神经元功能的见解，它们是 难以维持，需要大量的术后护理。 然而，在这方面， 单侧黑质纹状体DA耗竭的大鼠提供了一个非常有用的 帕金森病的动物模型 这些动物忽视刺激 出现在对侧身体表面或空间，并且当用 DA模拟药物显示出一种高度可量化的行为不对称性， 作为旋转（盘旋）行为。 最近，研究表明， 胎儿黑质或肾上腺髓质组织位于或靠近 失神经纹状体至少可以部分逆转这些行为 不对称。 迄今为止的证据表明，这些移植物 通过释放儿茶酚胺减轻DA耗竭的症状，但 这一假设从未被直接验证过。 在本申请中，我们 提出了一系列的实验。 在第一系列的实验中，我们建议开发一种推拉式的 灌流技术，以测量儿茶酚胺代谢物流出到 侧脑室作为儿茶酚胺释放的指标。 接下来我们就 比较胎儿黑质、肾上腺髓质或胎儿 将顶盖组织移植物置于侧脑室以释放 儿茶酚胺和/或儿茶酚胺代谢物进入侧脑室， 随着移植后时间的推移。 第三，我们将使用一系列 药理学操作，以确定：（1）是否有任何关系 富含儿茶酚胺的组织移植物释放 儿茶酚胺及其减弱旋转行为的能力 单方面DA耗竭产生的失衡;以及（2）是否有任何 控制儿茶酚胺释放的正常机制在组织中起作用 移植物