SEROTONIN AND HPA AXIS INTERACTIONS IN SUICIDE BRAINS

这是一份关于ADAMSHA SDA的提案，重点关注监管和 下丘脑-垂体-肾上腺（LHPA）轴与 5-羟色胺（5-HT）系统在人脑中的作用。 lHPA（或“脑”）功能障碍 压力”）轴和5-HT）系统是两个最强的发现， 抑郁和自杀 从动物研究中得知， 以各种方式相关，并且来自两个系统的分子 共同定位在大脑区域，如边缘系统，包括 海马体和下丘脑，以及中缝背侧和正中 原子核 这项建议的基本目标是研究 LHPA脑应激轴与脑内5-HT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（具体 目标1和2）。 从动物研究中也知道， 和非常高的类固醇水平（LHPA的最终产物）轴）可能 会导致海马体神经细胞的缺失。 鉴于目前的情况 导致自杀可以被构造为一种慢性应激状态， 项目还将评估是否有任何神经病理学异常 自杀受害者的边缘系统（具体目标3），特别是 5-HT和lHPA相关分子富集区。 为了实现我们的目标，我们 将使用受体放射自显影，原位杂交，定量 形态计量学分析和免疫细胞化学定量：1. 5HT 受体结合和mRNA水平在边缘系统，下丘脑和 中缝核; 2. 糖皮质激素（GR）和盐皮质激素（MR）受体 mRNA水平在相同的区域; 3.促肾上腺皮质激素释放激素和 下丘脑精氨酸加压素mRNA水平; 4. 神经元损失 或者边缘系统的退化 我们将比较这些参数 在自杀受害者和意外死亡受害者之间（年龄匹配， 性别和死亡时间）。 利用“心理解剖”收集 相关临床信息，我们将评估：1。 如果这些变化 系统是抑郁症特有的，或者在所有自杀受害者身上都能找到。 无论诊断和2。 什么是影响临床和 人口统计学因素对这些生化参数的影响（年龄、性别、病程 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.).