SEROTONIN AND HPA AXIS INTERACTIONS IN SUICIDE BRAINS

这是一项关于ADAMSHA SDA的建议，其重点是监管和 下丘脑-垂体-肾上腺轴与下丘脑-垂体-肾上腺轴的相互作用 人脑中的5-羟色胺(5-HT)系统。LHPA(或“脑”)功能障碍 应力“)轴和5-羟色胺系统)是最强的两个发现 抑郁症和自杀。从动物研究中得知，它们是 以各种方式联系在一起，来自这两个系统的分子 共同定位于大脑区域，如边缘系统，包括 海马体和下丘脑，以及中缝背侧和正中缝 原子核。这项建议的根本目的是研究 LHPA脑应激轴与脑内5-羟色胺系统的相互作用 使用生化和神经解剖学工具的自杀受害者(特定 目标1和2)。从动物研究中也知道，慢性应激 而非常高的类固醇水平(LHPA轴的最终产物)可能 导致海马区神经细胞丢失。因为在这种情况下 导致自杀可以被构建为一种慢性压力状况，这一点 该项目还将评估是否存在任何神经病理异常 在自杀受害者的边缘系统(具体目标3)，特别是在 这些区域富含5-羟色胺和LHPA相关分子。为了实现目标，我们 将使用受体放射自显影，原位杂交，定量 形态计量学和免疫细胞化学定量：1.5羟色胺 边缘系统、下丘脑和下丘脑的受体结合和mRNA水平 中缝核团；2.糖皮质激素(GR)和盐皮质激素(MR)受体 3.促肾上腺皮质激素释放激素和 精氨酸加压素在下丘脑中的表达；4.神经元丢失 边缘系统有变性。我们将比较这些参数 自杀受害者和意外死亡受害者之间(年龄匹配， 性别和验尸时间)。利用“心理尸检”收集 相关的临床资料，我们将评估：1.如果这些变化 系统是专用于抑郁症的，或者在所有自杀受害者身上都有 与诊断无关，以及2.临床和 人口统计因素对这些生化参数(年龄、性别、持续时间)的影响 疾病等)。

This is a proposal for an ADAMSHA SDA which focuses on the regulation and interaction of the Hypothalamic-Pituitary-Adrenal (LHPA) axis and the Serotonin (5HT) system in human brain. Dysfunction of the lHPA (or "brain stress") axis and of the 5HT) system are two of the strongest findings in both depression and suicide. It is known from animal studies that they are related in a variety of ways and that molecules from the two systems are co-localized in brain regions such as the limbic system, including the hippocampus and the hypothalamus, as well as in the dorsal and median raphe nucleus. The fundamental goal of this proposal is to study the interactions of the LHPA brain stress axis and the 5HT system in the brains of suicide victims using biochemical and neuroanatomical tools (specific aims 1 & 2). It is also known from animal studies that both chronic stress and very high steroid levels (the final product of the LHPA) axis) may cause neuronal cell loss in the hippocampus. Since the circumstances leading to suicide can be constructed as a chronic stress condition, this project will also evaluate if there are any neuropathological abnormalities in the limbic system of suicide victims (specific aim 3), in particular in the areas rich in 5HT and lHPA related molecules. To achieve our goals, we will use receptor autoradiography, in situ hybridization, quantitative morphometric analysis and immunocytochemistry to quantify: 1. 5HT receptor binding and mRNA levels in the limbic system, hypothalamus and raphe nuclei; 2. glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA levels in the same regions; 3. corticotropin releasing hormone and arginine vasopressin mRNA levels in the hypothalamus; 4. neuronal loss an/or degeneration in the limbic system. We will compare these parameters between suicide victims and accidental death victims (matched for age, gender and post-mortem time). Using "psychological autopsies" to gather relevant clinical information, we will assess: 1. if changes in these systems are specific for depression, or are found in all suicide victims irrespective of diagnosis and 2. what is the influence of clinical and demographic factors on these biochemical parameters (age, gender, duration of illness, etc.).