FETAL ALCOHOL AND NEUROIMMUNE NETWORKS

胎儿酒精和神经免疫网络

• 批准号: 3113257
• 负责人: ZEHAVA GOTTESFELD
• 金额: $ 19.03万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3113257
• 关键词: adrenocorticotropic hormone; brain metabolism; fetal alcohol syndrome; humoral immunity; inborn immunodeficiency; interleukin 1; laboratory rat; neurochemistry; neuroimmunomodulation; neurons; neurophysiology; pituitary adrenal axis

The overall objective of the proposed studies is to understand mechanisms by which prenatal alcohol exposure can lead to lasting immune deficits. Compelling evidence has indicated that the central nervous system utilizes neuroendocrinologic and autonomic neural pathways to modulate immune responses to immunogenic challenges. The proposed hypothesis is that exposure to alcohol in utero alters brain responsiveness to cytokine- mediated immune signals and, thus, changes the course of normal immune responses. The specific aims are: first, to characterize effects of prenatal alcohol exposure on brain responsiveness to antigenic challenges; and second, to compare the cerebral responses to immune activation with those elicited by cytokines (e.g. interleukin-1). The subjects, young-adult rats exposed to prenatal alcohol or the appropriate pair-fed controls, will be treated with antigens, interleukin- 1, or the respective vehicles. At various times post-treatment, brain responsiveness to the treatments will be assessed by the activity of: (1) central noradrenergic innervation of discrete brain regions; (2) sympathetic neural projections to lymphoid organs ("sympatho-lymphoid axis"), and (3) the pituitary-adrenocortical humoral axis. Activity of cerebral and sympathetic noradrenergic neurons will be determined by norepinephrine metabolism in the target region. The functional date of the pituitary-adrenal axis will be evaluated by plasma concentrations of adrenocorticotropic hormone and corticosterone. The neurochemical and endocrinologic changes will be correlated with the immune response to the various treatments. The proposed studies will advance our understanding of mechanisms by which prenatal alcohol exposure alters communication between the immune and central nervous system, that may compromise the well-being of the host.

拟议研究的总体目的是了解机制 产前酒精暴露会导致持久的免疫缺陷。 令人信服的证据表明，中枢神经系统利用 神经内分泌和自主神经途径调节免疫 对免疫原性挑战的反应。拟议的假设是 子宫中酒精暴露会改变大脑对细胞因子的反应性 - 介导的免疫信号，因此改变了正常免疫的过程 回答。具体目的是：首先，表征 大脑对抗原挑战的反应性的产前酒精暴露； 其次，将对免疫激活的大脑反应与 细胞因子引起的那些（例如白介素-1）。 受试者，暴露于产前酒精的年轻大鼠或 适当的配对对照，将用抗原，白介素治疗 1，或各自的车辆。在处理后的不同时间，大脑 对治疗的反应将由以下活动进行评估：（1） 离散大脑区域的中央去甲肾上腺素能神经支配； （2） 淋巴器官的交感神经预测（“交感神经 - 淋巴机） 轴”），（3）垂体 - 肾上腺皮质体液轴。 脑和交感的去甲肾上腺素能神经元将由 目标区域中的去甲肾上腺素代谢。 功能日期 垂体 - 肾上腺轴将通过血浆浓度评估 肾上腺皮质激素和皮质酮。 神经化学和 内分泌的变化将与对 各种治疗方法。 拟议的研究将提高我们对机制的理解 产前酒精暴露改变了免疫之间的交流 中枢神经系统，这可能会损害宿主的福祉。