MECHANISMS OF STRESS SPECIFIC CHANGES IN GENE EXPRESSION

基因表达中应激特异性变化的机制

• 批准号: 6078395
• 负责人: Esther Louise Sabban
• 金额: $ 3.06万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078395
• 关键词: DNA binding protein; adrenal medulla; cAMP response element binding protein; enzyme induction /repression; epinephrine; gel mobility shift assay; gene expression; genetic regulatory element; genetically modified animals; in situ hybridization; laboratory mouse; laboratory rat; locus coeruleus; neuroendocrine system; norepinephrine; stress; sympathetic ganglion; transcription factor; western blottings

DESCRIPTION Early responses to stress include activation of noradrenergic neurons of the locus coeruleus, and the sympathetic neuronal and adrenomedullary systems, resulting in production of the central and peripheral catecholamines norepinephrine and epinephrine. Stress also elevates gene expression for catecholamine biosynthetic enzymes, and there are gene-, tissue-, and stressor-specific differences in these responses to stress. The proposal investigates the mechanisms of regulation of gene expression of catecholamine biosynthetic enzymes (TH, DBH, and PNMT) in vivo in the adrenal medulla, sympathetic ganglia, and in different brain areas of rats exposed acutely, repeatedly or chronically to various stressors. Specific aims are: (1) determine effects of different stressors on TH, DBH, and PNMT gene expression, (2) determine dependence of single or repeated stress-elicited effects of TH, DBH, and PNMT expression on the transcription factor c-fos, (3) characterize the basis for differential regulation of TH and DBH gene expression in sympathetic ganglia compared to adrenal medulla, (4) determine effects of prior chronic or repeated exposure to stressors in the response to a novel stressor and (5) determine if TH and DBH gene expression is detectable in brain areas other than the major catecholaminergic cell fields, and if expression in these areas is regulated by stressors.

描述 对应激的早期反应包括激活去甲肾上腺素能神经元 蓝斑、交感神经元和肾上腺髓质 系统，导致中央和外围设备的生产 儿茶酚胺、去甲肾上腺素和肾上腺素。压力也会提升基因 儿茶酚胺生物合成酶的表达，并有基因-， 这些对压力的反应因组织和应激源而异。 该提案调查了基因表达调控的机制。 体内儿茶酚胺生物合成酶(TH、DBH和PNMT)的研究 大鼠肾上腺髓质、交感神经节及不同脑区 剧烈地、反复地或长期地暴露在各种压力源之下。特定的 目的是：(1)确定不同应激源对胸径、胸径和胸径的影响 PNMT基因表达，(2)确定单次或重复依赖 TH、DBH和PNMT的表达对应激诱导的影响 转录因子c-fos，(3)表征差异的基础 交感神经节TH和DBH基因表达调控的比较 对于肾上腺髓质，(4)确定既往慢性或反复的影响 在对新的压力源的反应中暴露于压力源和(5) 确定TH和DBH基因在大脑其他区域是否可检测到表达 比主要的儿茶酚胺能细胞场，如果在这些细胞中表达 区域受压力源的调节。