Cellular Electrophysiology of Nicotine Addiction Clinical Phenotypes

尼古丁成瘾临床表型的细胞电生理学

• 批准号: 8420444
• 负责人: RICARDO A FELDMAN
• 金额: $ 18.42万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8420444
• 关键词: 15q25; Action Potentials; Alleles; Amygdaloid structure; Anterior; Back; Biopsy; Brain; Brain imaging; Cell Line; Cells; Cessation of life; Clinical; Derivation procedure; Disease; Dopamine; Dopamine Agonists; Dorsal; Electrophysiology (science); Etiology; Exhibits; Frequencies; Gene Cluster; Gene Frequency; Genes; Genetic; Genotype; Glossary; Goals; Human; Image; In Vitro; Link; Measures; Minor; Mutation; Neurons; Neurosciences; Nicotine; Nicotine Dependence; Nicotinic Agonists; Nicotinic Receptors; Patients; Phenotype; Preclinical Drug Evaluation; Predictive Value; Property; Research; Rest; Risk; Scientist; Severities; Single Nucleotide Polymorphism; Skin; Smoker; Smoking; Testing; Tyrosine 3-Monooxygenase; Validation; Variant; Ventral Striatum; Whole-Cell Recordings; addiction; base; clinical phenotype; dopaminergic neuron; endophenotype; established cell line; induced pluripotent stem cell; innovation; method development; nerve stem cell; non-smoker; receptor function; response; smoking cessation

DESCRIPTION (provided by applicant): Smoking remains the leading cause of preventable diseases and death in the US, and is known to be heritable. This application aims to develop a set of nicotine addiction cell lines based on clinically defined imaging phenotype and genotype. Our goal is to test that neuronal electrophysiological response to nicotinic agonists will be associated with the strength of the clinical imaging based circuit phenotype in patients with severe nicotine addiction and carry smoking related risk alleles. Our innovation here is to closely link these cell lines with state-of-the art clinical measures of nicotine addiction, so that we coud iteratively test electrophysiological phenotypes of the cells that are likely underlying key clinicl nicotine addiction measures.

描述（由申请人提供）：吸烟仍然是美国可预防疾病和死亡的主要原因，并且已知是可遗传的。本申请旨在基于临床定义的成像表型和基因型开发一组尼古丁成瘾细胞系。我们的目标是测试神经元对烟碱激动剂的电生理反应将与严重尼古丁成瘾并携带吸烟相关风险等位基因的患者中基于临床成像的回路表型的强度相关。我们的创新在于 将这些细胞系与尼古丁成瘾的最新临床测量方法联系起来，这样我们就可以反复测试细胞的电生理表型，这些表型可能是关键的临床尼古丁成瘾测量方法的基础。