SGER: Quantitative Mapping of Se and Associated Proteins in the Brain: Effects of Dietary Deficiency

硒（Se）是一种非金属必需微量元素，通过氨基酸硒半胱氨酸结合到不同的硒蛋白中发挥多种生物效应。在大脑中，硒蛋白保护神经组织免受氧化应激并维持正常的甲状腺激素功能。硒仅通过饮食摄入，摄入不足会导致许多生理和心理上的缺乏症状，包括异常的行为反应。由于野生动物和家畜依赖于环境来源的硒，低土壤含量使这些动物种群面临严重的不利影响风险。中枢神经系统（CNS）的独特之处在于，在饮食不足的情况下，硒的净水平保持不变，而不是减少，并且在这种状态下，选定的硒蛋白水平会提高。这一证据表明硒对于优化神经功能至关重要，并且适应性机制保护中枢神经系统免受环境缺陷的影响。该SGER项目将利用神经解剖学和核物理学的互补专业知识来绘制硒及其蛋白质在大脑中的细胞分布，以确定在该器官内区域和细胞类型特异性模式中具有特征功能的特定含硒半胱氨酸蛋白质的保存是否与缺乏硒时大脑功能的维持相关。在这里开发的完全独特的原位化学分析方法具有前所未有的灵敏度，将允许在大脑复杂的细胞结构组织背景下检测这种生物无机元素，并有望显著推进基础知识，并激发对硒剥夺对细胞和系统水平脑功能的影响及其对中枢神经系统发育，可塑性和衰老的相关影响的新兴趣。

Selenium (Se) is a nonmetallic essential trace element that exerts numerous biological effects through incorporation into distinct selenoproteins via the amino acid, selenocysteine. In the brain, selenoproteins protect neural tissue from oxidative stresses and maintain normal thyroid hormone function. Available solely through dietary intake, insufficient ingestion of Se leads to numerous physiological and psychological symptoms of deficiency, including abnormal behavioral responses. Since wildlife, as well as domestic livestock, depend upon environmental sources of Se, low soil levels puts these animal populations at significant risk for adverse effects. The central nervous system (CNS) is unique in that net levels of Se are maintained, not diminished during dietary insufficiency, and that levels of select selenoproteins are enhanced during such states. This evidence suggests that Se is critical for optimal neurological function, and that adaptive mechanisms protect the CNS from environment deficits. This SGER project will utilize complementary expertise in neuroanatomy and nuclear physics to map the cellular distribution of Se and its proteins in the brain, to determine if preservation of specific selenocysteine-containing proteins of characterized function in region- and cell type-specific patterns within this organ is correlated with maintenance of brain function during deficiency. The unprecedented sensitivity of the wholly-unique in situ chemical analytical approach developed here will permit this bioinorganic element to be detected within the context of the complex cytoarchitectural organization of the brain, and is expected to significantly advance fundamental knowledge and stimulate new interest in the outcome of Se-deprivation on cellular- and systems levels-level brain function and its related impact on CNS development, plasticity, and senescence.