Nicotinic Receptors in Parkinson's Disease

帕金森病中的烟碱受体

• 批准号: 6876627
• 负责人: MARYKA QUIK
• 金额: $ 33.58万
• 依托单位: PARKINSON'S INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876627
• 关键词: Parkinson' s disease; Saimiri; antiparkinson drugs; autoradiography; basal ganglia; brain disorder chemotherapy; corpus striatum; disease /disorder model; dopamine; immunocytochemistry; in situ hybridization; laboratory mouse; neuropsychology; neurotransmitter agonist; nicotinic receptors; nonhuman therapy evaluation; substantia nigra

DESCRIPTION (provided by applicant): Our goal is to determine the role of nicotinic receptor subtypes in the basal ganglia with the long-term objective of developing novel therapeutic strategies for Parkinson's disease. The rationale for this work is based on studies showing that nicotine administration improves locomotor deficits after a nigrostriatal lesion and, furthermore, that nicotine or smoking results in an apparent protective effect against nigrostriatal damage in rodents and in Parkinson's disease. However, multiple nicotinic receptors are activated by nicotine to result in beneficial but also side effects in both the peripheral and central nervous system. We hypothesize that specific nicotinic receptor populations in the brain are involved based on work demonstrating that the distinct subtypes have unique localization and molecular functions. We will approach these studies through four specific aims. As a crucial first step, we will identify the regional and cellular localization of nicotinic receptor subtypes in basal ganglia and determine the changes in receptor subtypes after nigrostriatal degeneration. This will be done using three different approaches including in situ hybridization, receptor autoradiography and immunocytochemistry and form the basis of Specific Aims 1 and 2. We will then initiate studies to assess the nicotinic receptor subtypes involved in striatal function as described in Specific Aim 3, followed by behavioral studies (Specific Aim 4) to determine the ability of nicotinic agonists to reverse parkinsonism. This work should increase our understanding of the role of different nicotinic receptor subtypes in basal ganglia function. In summary, the proposed work should provide new insight concerning alterations in nicotinic receptor subtypes after nigrostriatal damage and nicotinic agonist treatment. These data together with the results of the behavioral studies may form a basis for the use of nicotinic drugs in the treatment of Parkinson's disease.

描述（由申请人提供）：我们的目标是确定烟碱受体亚型在基底神经节中的作用，其长期目标是为帕金森氏病开发新的治疗策略。这项工作的基本原理是基于研究表明，尼古丁给药可改善黑质性病变后的运动缺陷，此外，尼古丁或吸烟会导致对啮齿动物和帕金森氏病的黑骨损害的明显保护作用。然而，尼古丁激活多种烟碱受体，从而导致有益，但在周围神经系统和中枢神经系统中也副作用。我们假设大脑中的特定烟碱受体群体是基于工作，表明不同的亚型具有独特的定位和分子功能。我们将通过四个具体目标对这些研究进行研究。作为至关重要的第一步，我们将确定基底神经节中烟碱受体亚型的区域和细胞定位，并确定黑质层变性后受体亚型的变化。这将使用三种不同的方法来完成，包括原位杂交，受体自显影和免疫细胞化学，并构成了特定目标1和2的基础。然后，我们将开始研究以评估与特定行为研究（特定目标4）相关的烟碱和烟碱式态度parace的烟碱功能3所描述的型烟碱受体亚型。这项工作应增加我们对不同烟碱受体亚型在基底神经节功能中的作用的理解。 总而言之，拟议的工作应提供有关在黑质纹状体损伤和烟碱激动剂治疗后烟碱受体亚型改变的新见解。这些数据以及行为研究的结果可能是使用烟碱药物治疗帕金森氏病的基础。