Changes in nicotinic receptors in parkinsonian animals

帕金森病动物烟碱受体的变化

• 批准号: 6597568
• 负责人: JENNIFER M KULAK
• 金额: $ 4.42万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6597568
• 关键词: Parkinson's disease; Saimiri; autoradiography; corpus striatum; in situ hybridization; nicotinic receptors; postdoctoral investigator; receptor binding; smoking; substantia nigra; tobacco abuse

DESCRIPTION (provided by applicant): As an initial approach, the research proposed in this application will identify specific subtypes of nicotinic acetyicholine receptor (nAChR) present in the nigrostriatal system which may be investigated for development of novel therapeutics for treatment of Parkinson's disease. Evidence that nAChRs may provide a therapeutic target for treatment include: (i) the demonstration of an inverse relationship between smoking and the incidence of PD; (ii) alleviation of the locomotor symptoms of PD with nAChR agonist administration; (iii) selective changes in expression of nAChR mRNAs in squirrel monkeys lesioned with the nigrostnatal toxin MPTP; and (iv) preliminary results indicating alterations in nAChR binding in parkinsonian non-human primates. Nicotinic receptor subtypes expressed in the nigrostriatal system will be investigated using 1251-epibatidine, 3H-cytisine, and '251-a-bungarotoxin autoradiography and competition with subtype-selective IIAChR ligands in the substantia mgra, caudate, and putamen of control and parkinsonian monkeys and the neurotransmitter makeup to which specific subunits colocalize will be determined by dual label in situ hybridization in the substantia nigra.

描述（由申请人提供）： 作为初始方法，本应用程序中提出的研究将确定 存在于烟碱乙酸受体（NACHR）的特定亚型 可能会调查用于开发新颖的黑质体系 治疗帕金森氏病的治疗剂。纳赫人可能 提供治疗的治疗目标包括：（i） 吸烟与PD发病率之间的逆关系； （ii）减轻 NACHR激动剂给药的PD的运动症状； （iii） 松鼠猴子中NACHR mRNA表达的选择性变化 与nigrostnatal毒素MPTP一起； （iv）初步结果表明 帕金森非人类灵长类动物中NACHR结合的改变。烟 将研究在黑质系统中表达的受体亚型 使用1251- pepibatidine，3H-胞嘧啶和'251-A-Bungarotoxin放射自显影术 以及与底mgra中的亚型选择性IIACHR配体的竞争， 尾状，控制和帕金森猴的。tamen和 神经递质的化妆，特定亚基共定位为 通过双重标记在黑质中的原位杂交确定。