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: 2695501
• 负责人: Esther Louise Sabban
• 金额: $ 2万
• 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/2695501
• 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 对压力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，从而产生中央和外围 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，并且有基因， 这些对压力的反应存在组织和压力源特异性差异。 该提案研究了基因表达的调控机制 体内儿茶酚胺生物合成酶（TH、DBH 和 PNMT）的 肾上腺髓质、交感神经节以及大鼠的不同大脑区域 急性、反复或长期暴露于各种压力源。具体的 目标是：(1) 确定不同压力源对 TH、DBH 和 DBH 的影响 PNMT基因表达，（2）确定单次或重复的依赖性 TH、DBH 和 PNMT 表达对应激引起的影响 转录因子 c-fos，(3) 表征差异的基础 交感神经节 TH 和 DBH 基因表达的调节比较 对肾上腺髓质，（4）确定先前慢性或重复的影响 暴露于应激源以应对新的应激源以及 (5) 确定 TH 和 DBH 基因表达是否可在大脑其他区域检测到 比主要的儿茶酚胺能细胞区域，并且如果在这些区域中表达 区域受到压力源的调节。