Neurohypophysial control of the cytokine stress response

描述（由申请人提供）：身体健康状况的下降降低了精神疾病患者的生活质量，增加了死亡率。精神病理学影响全身健康的身心途径（例如，促进代谢和心血管疾病的发展）尚不清楚。细胞因子产生的改变存在于抑郁症、创伤后应激障碍（PTSD）和慢性压力中，它代表了大脑影响身体健康的潜在途径。申请人的总体研究目标是提供大脑，压力和细胞因子调节之间相互关系的机制解释。本研究的目的是探讨大脑控制细胞因子对急性应激反应的潜在途径，即下丘脑-神经垂体系统（HNS）的细胞因子释放。il -1 β和IL-6是与疾病进展有关的细胞因子，在视上核和室旁核的大细胞神经元中表达，并储存在垂体后叶中。尽管il -1 β和il -6在下丘脑神经元的控制下被定位为分泌到全身循环中，但尚不清楚这种储存的细胞因子池是否可以被招募来影响血液细胞因子浓度。本研究旨在验证细胞因子对急性应激源的反应是由HNS中产生细胞因子的神经元控制的假设。为了实现这一提议的目标，提出了两个目标：1)目标1将检验HNS是细胞因子对心理应激反应所必需的假设；2)目的2将验证SON和PVN的细胞因子阳性神经元具有应激反应的假设。这些研究的完成将证明HNS是否控制细胞因子对心理应激的反应，并将确定应激对HNS中细胞因子表达的影响。意义：在患有精神疾病的个体中，炎症状态的增加被认为在疾病进展中起作用。大脑控制通路被认为影响炎症状态，但尚未明确确立。本研究计划测试大脑控制炎症的机制。

DESCRIPTION (provided by applicant): A decline in physical health decreases quality of life and increases mortality rate for individuals with mental illness. The mind-body pathway(s) by which psychopathologies affect whole body health, e.g.,contribute to the development of metabolic and cardiovascular disease, are unclear. Altered cytokine production is present in depression, post-traumatic stress disorder (PTSD) and chronic stress, and represents a potential pathway by which the brain could affect physical health. The overall research objective of the applicant is to provide a mechanistic explanation of the interrelations between brain, stress and cytokine regulation. The research objective of this proposal is to examine a potential pathway by which the brain could control the cytokine response to acute stressors, i.e., cytokine release from the hypothalamo-neurohypophysial system (HNS). IL-1beta and IL-6, cytokines implicated in disease progression, are expressed in the magnocellular neurons of the supraoptic and paraventricular nuclei and stored in the posterior pituitary. Although IL-1beta and IL-6are positioned to be secreted into the general circulation under the control of the hypothalamic neurons, it is not known if this stored cytokine pool can be recruited to affect blood cytokine concentrations. This proposal is designed to test the hypothesis that the cytokine response to acute stressors is controlled by cytokine-producing neurons in HNS. Two aims are proposed to accomplish the objective of this proposal: 1) Aim 1 will test the hypothesis that the HNS is necessary for the cytokine response to psychological stress; and 2) Aim 2 will test the hypothesis that the cytokine positive neurons of the SON and PVN are stress responsive. The completion of these studies will demonstrate whether the HNS controls the cytokine response to pyschological stress and will determine the effect of stress on cytokine expression in theHNS. Singnificance: There is a increase in the inflammatory state in individuals with mental illness that is thought to play a role in disease progression. Brain control pathways are thought to affect the inflammatory state but are not clearly established. This research proposal tests a mechanism of brain control of inflammation.