Fluorescence Imaging of Active Molecules Associated with Depression^★

Abstract

Depression is a typical condition of depressive disorder, which takes great burden to family and society. However, the current uncertainty about the etiology and pathogenesis has greatly hindered the development of effective antidepressant drugs. Changes in the levels of active molecules associated with depression, such as reactive oxygen species, neurotransmitters and proteins, play a key role in the occurrence and development of depression. Therefore, detection of active molecules related to depression is particularly important for understanding the pathogenesis of depression. Fluorescence imaging has the advantages of high sensitivity, intuition, in situ, real-time, etc. Therefore, fluorescence imaging technology has become an effective method to monitor the active molecules related to depression. Researchers have effectively detected these active molecules using fluorescence imaging. The recent progress in fluorescence imaging detection of reactive oxygen species (ROS), monoamine neurotransmitters and monoamine oxidase in the active molecules associated with depression in the past five years are reviewed with focus on the development of fluorescence probes and prospects. Keywords depression; fluorescence imaging; reactive oxygen species (ROS); neurotransmitter; enzyme 1 引言 抑郁症是一种情绪障碍, 具有极高的发病率和致死 致残率, 为家庭和社会带来了极大的精神和经济负担 [1] . 核心症状是情绪低落、快感缺乏、易怒、难以集中注意 力、食欲和睡眠异常等 [2] . 若要实现抑郁症的有效预防 和治疗, 必须对抑郁症的发生和发展过程进行彻底的了 解. 然而, 目前抑郁症因其致病因素复杂、病因不清及 发病机制不详, 一直是神经科学领域的一大难题. 现有 研究结果表明, 抑郁症相关的活性分子包括神经递质、 相应的合成或水解酶、活性氧自由基(ROS)等, 在抑郁 症的发生发展过程中发挥至关重要作用 [3][4] .大脑因其耗氧量高, 脂肪含量丰富, 极易发生氧化 应激且对氧化应激尤为敏感 [5] . 研究表明, 大脑中氧化 应激即 ROS 过量产生, 造成大量蛋白质、 核酸等生物大 分子的损伤, 从而导致抑郁症的发生与发展. 如 Maes 课题组 [6] 指出重度抑郁症的患者体内 ROS、过氧化物和 黄嘌呤氧化酶等氧化性物质水平显著增加, 而维生素 E、锌和辅酶 Q10 等一些关键抗氧化剂的浓度以及谷胱 甘肽过氧化物酶(GPX)等抗氧化酶活性明显降低; Bilici 课题组 [7] 发现抑郁症患者血液中的 ROS 含量较高, 同时 抗氧化酶活性和脂质过氧化水平增高, 作者认为可能是 免疫炎症应答的激活、单胺类物质的分解代谢和异常脂 质化合物导致了 ROS 的过量产生. 同时, 5-羟色胺 (5-HT)、多巴胺(DA)和去甲肾上腺素(NE)等神经递质在 大脑正常生理活动中起到重要作用. 例如 Schildkraut