Role of 5-HT1A-AR overexpression in affective disorders

5-HT1A-AR 过度表达在情感障碍中的作用

• 批准号: 6994244
• 负责人: Miles Berger
• 金额: $ 3.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994244
• 关键词: REM sleep; autoradiography; behavior test; behavioral /social science research tag; behavioral genetics; circadian rhythms; disease /disorder model; dorsal raphe nucleus; electroencephalography; electrophysiology; frontal lobe /cortex; gene expression; genetically modified animals; hippocampus; immunocytochemistry; laboratory mouse; major depression; microdialysis; neural transmission; predoctoral investigator; psychopathology; serotonin; serotonin inhibitor; serotonin receptor

DESCRIPTION (provided by applicant): Major depression is a common mental illness thought to arise in part from decreased serotonin (5-HT) neurotransmission. Recent evidence suggests that this decrease may arise from increased expression of inhibitory 5-HT1A autoreceptors (5-HT1A-AR) on 5-HT neurons. To model this aspect of the pathophysiology of depression, I have created transgenic mice designed to overexpress 5-HT1A-AR; I hypothesize that these mice will have decreased 5-HT transmission and depressive-like behavior. Aim 1: Validate 5-HT1A-AR overexpression in transgenic mice by quantitative autoradiography and immunocytochemistry. Aim 2: Determine the effect of 5-HT1A-AR overexpression on 5-HT neurotransmission by in vivo microdialysis and electrophysiology. Aim 3: Determine the effect of 5-HT1A-AR overexpression in tests of neurovegetative function and depressive-like behavior. These studies should increase our understanding of the underlying causes of depression and other affective disorders, and may lead to new treatment strategies for patients suffering from these disorders.

描述（由申请人提供）：重度抑郁症是一种常见的精神疾病，部分原因是血清素 (5-HT) 神经传递减少。 最近的证据表明，这种减少可能是由于 5-HT 神经元上抑制性 5-HT1A 自身受体 (5-HT1A-AR) 表达增加所致。为了模拟抑郁症病理生理学的这一方面，我创建了转基因小鼠，旨在过度表达 5-HT1A-AR；我推测这些小鼠的 5-HT 传递会减少并出现抑郁样行为。 目标 1：通过定量放射自显影和免疫细胞化学验证转基因小鼠中 5-HT1A-AR 的过表达。 目标 2：通过体内微透析和电生理学确定 5-HT1A-AR 过表达对 5-HT 神经传递的影响。目标 3：确定 5-HT1A-AR 过度表达在植物神经功能和抑郁样行为测试中的影响。这些研究应该会增加我们对抑郁症和其他情感障碍的根本原因的理解，并可能为患有这些疾病的患者带来新的治疗策略。