PSYCHONEUROIMMUNONODULATION IN AGING

衰老过程中的心理神经免疫调节

• 批准号: 3475643
• 负责人: DENISE L BELLINGER
• 金额: $ 12.1万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3475643
• 关键词: T lymphocyte; aging; animal ecology; animal old age; autonomic nervous system; biological signal transduction; cell death; cellular immunity; flow cytometry; immunocytochemistry; immunopharmacology; innervation; laboratory rat; nerve endings; neuropeptides; neurotransmitter metabolism; neurotransmitter receptor; norepinephrine; psychoneuroimmunology; spleen; sympathetic nervous system; tissue /cell culture

DESCRIPTION (Applicant's Abstract): Evidence from a wide variety of fields indicates that both neural modulation of immunity and immune-mediated communication with the CNS represent important pathways of biological signalling with importance to human health and disease throughout life. With the normal aging process the frequency of viral infections, cancer, and autoimmune diseases increases, cell-mediated immune responses decline, degenerative brain changes occur, and psychosocial factors appear to have a greater impact of health. Recent studies from this laboratory have demonstrated a striking decrease in the presence of noradrenergic (NA) nerve fibers and norepinephrine (NE) availability in spleens from aged rodents that correlate well with the decline in T cell mediated immunity that occurs with aging. Concomitant with this age-related decline in NA splenic innervation, the density of specific immune cell populations in compartments that receive abundant NA nerve fibers in the young adult spleen also shows a progressive decline with age. Collectively, these findings suggest a possible relationship between age-associated denervation of NA innervation of secondary lymphoid organs and age-associated immunosenescence. The present proposal is designed to further investigate the dynamics of NA innervation in the aged spleen and its relationship to immunocompetence in aged rodents. Specific Aim 1 addresses the availability of NE for interaction with splenocytes and the ability of splenocytes to respond to NA sympathetic signals in aged rat. Specific Aim 2 proposes to determine whether loss of NA nerve fibers in old spleens result from (1) a retraction of NA nerve fibers with age, (2) a metabolic deficit that depletes NE from nerve terminals, or (3) cell death of NA sympathetic neurons in the superior mesenteric-celiac ganglionic complex. Specific Aim 3 is to examine the capability of the old spleen to maintain NA innervation. Specific Aim 4 is to investigate the effect of chronic environmental antigenic stimulation on the full expression of age-associated decline in NA innervation of the spleen. These studies examine a vital part of the neural-immune link, efferent autonomic outflow to lymphoid organs, at a time when cell mediated immunity is compromised. They will provide a better understanding of the functional consequences of diminished neural signals on immune function in aged rodents and may ultimately lead to new therapeutic approaches for immunomodulation in conditions of compromised immune function through pharmacologic manipulation of neurotransmitter systems.

描述（申请人的摘要）：来自各个领域的证据 表明免疫的神经调节和免疫介导 与中枢神经系统的通讯是生物信息的重要途径 信号对人类一生的健康和疾病具有重要意义。 随着正常的衰老过程，病毒感染、癌症、 自身免疫性疾病增加，细胞介导的免疫反应下降， 大脑发生退行性变化，社会心理因素似乎对 对健康的影响更大。 该实验室最近的研究表明 去甲肾上腺素能 (NA) 的存在显着减少 老年人脾脏中神经纤维和去甲肾上腺素 (NE) 的可用性 与 T 细胞介导的免疫力下降密切相关的啮齿类动物 随着衰老而发生。 与年龄相关的 NA 下降相伴随 脾脏神经支配，特定免疫细胞群的密度 年轻人中接受丰富的 NA 神经纤维的隔室 脾脏也随着年龄的增长而逐渐衰退。 总的来说，这些 研究结果表明年龄相关的去神经支配之间可能存在关系 次级淋巴器官的 NA 神经支配与年龄相关 免疫衰老。 本提案旨在进一步调查 老年脾脏NA神经支配的动态及其与 老年啮齿动物的免疫能力。 具体目标 1 解决了 NE 与脾细胞相互作用的可用性以及 脾细胞对老年大鼠的 NA 交感神经信号作出反应。 具体目标 2建议确定陈旧脾脏中NA神经纤维是否丢失 由于 (1) NA 神经纤维随着年龄的增长而回缩，(2) 代谢 神经末梢的 NE 缺失，或 (3) NA 细胞死亡 肠系膜上腹腔神经节复合体中的交感神经元。 具体目标3是检查旧脾的维持能力 NA 神经支配。 具体目标 4 是研究慢性病的影响 环境抗原刺激对完整表达的影响 与年龄相关的脾 NA 神经支配下降。 这些研究 检查神经免疫联系的重要部分，传出自主神经流出 当细胞介导的免疫力受到损害时，淋巴器官就会受到影响。 他们将提供对功能后果的更好理解 老年啮齿动物免疫功能的神经信号减弱，可能 最终导致免疫调节的新治疗方法 通过药物作用导致免疫功能受损的情况 神经递质系统的操纵。