IRON DEFICIENCY AND DOPAMINE

这项研究的主要长期目标将是确定 缺铁导致多巴胺代谢的功能改变 这项研究将确定，如果一个人 铁期间局部脑铁含量之间确实存在关系 缺乏，多巴胺功能障碍，和行为改变。此外， 这将在后期缺铁的情况下进行检查 哺乳与断奶后缺铁的关系。据估计为25亿 人类受到饮食中铁含量过少的影响；当 这发生在早期发育缺陷的认知和 行为发育经常发生。因此，我们可以理解 神经生物机制的发育时间和方面似乎 危急时刻。我们最近在一只断奶后的大鼠身上证实了铁 会迅速从大脑中消失，并可以迅速恢复 重新进食。铁并不是平均地丢失或恢复到地球的所有部分 大脑在耗尽和再耗尽期间。在纹状体中，有一个 铁损失超过30%，上升超过50% 胞外多巴胺(DA)。两者都用铁快速正火 心理治疗。具体地说，我们建议：1)确定活体内的变化 大鼠关键的多巴胺能通路中的多巴胺动力学，2)决定 如果局部脑缺铁改变释放和重新摄取 在来自尾壳核的突触体中的DA，并确定 这些转运蛋白的功能转运蛋白mRNA的改变，3) 确定是否存在与DA相关的行为(探讨其 环境和“焦虑”)受铁状况差的影响，以及4) 确定铁水平不足的发育时间(断奶前 断奶后的诗句)在调节这些影响方面很重要。这个 正在测试的假设是，哺乳后期的ID(PND10-21)将 对DA生物学和行为的影响比强制实施ID时更大 断奶后。我们还将确定这种影响是否不可逆转。 用后来的铁剂疗法。这些实验的预期结果将 证明DA从神经元间隙的清除是 腹侧中脑缺铁致衰弱 DA传输器的运行数量。以DA为单位的此高程 转向会导致环境探索性行为的减少 铁缺乏个体的“唤醒”。我们预计这些研究将 为未来的细胞直接效应研究奠定基础 局部脑铁对神经递质功能，大脑组织， 和细胞对营养缺乏的适应，这意味着 认知和行为发展。这项工作的意义在于 它研究了理解行为的生物学基础 在成百上千的铁中经常观察到的变化 世界各地的贫困儿童。

The principal long term goal of this research will be to determine if iron deficiency leads to functional changes in dopamine metabolism with a resultant impact on behavior This study will establish if a relationship does exist between regional brain iron content during iron deficiency, dopamine dysfunction, and behavioral alterations. Moreover, this will be examined within he context of iron deficiency during late lactation verses iron deficiency post weaning. An estimated 2.5 billion humans suffer from the effects of too little iron in their diet; when this occurs during early development deficits in cognition and behavioral development frequently occur. Thus an understanding of the developmental timing and aspects of the neurobiologic mechanisms seem critical. We have recently established in a post weaning rat that iron is rapidly lost from the brain and can be rapidly restored with refeeding. Iron is not lost or restored equally to all parts of the brain during depletion and repletion. In the striatum, there is a greater than 30 percent loss in iron and greater than 50 percent rise in extra-cellular dopamine (DA). Both are rapidly normalized with iron therapy. Specifically, we propose to: 1)identify alterations in in vivo dopamine kinetics in a key dopaminergic pathway of the rat, 2) determine if regional brain iron deficiency alters the release and re-uptake of DA in synaptosomes from caudate-putamen and to determine if the number of functioning transporter mRNA for these transporters are altered, 3) determine if t o kinds of DA related behaviors (exploration of their environment and "anxiety") are affected by poor iron status, and 4) determine if developmental timing of inadequate iron levels (pre-weaning verses post weaning) is important in mediating these effects. The hypothesis being tested is that ID during late lactation (PND10-21) will have a greater impact on DA biology and behavior than when ID is imposed post-weaning. We also will determine if this effect is irreversible with later iron therapy. The expected results of these experiments will demonstrate that DA clearance from the inter-neuronal space is attenuated by iron deficiency in ventral midbrain due to decreased amounts of functioning of the DA transporter. This elevation in DA in turn leads to decreased exploratory behavior of the environment and "arousal" of the iron deficient individual. We expect these studies to lay the groundwork for future cellular studies of direct effects of local brain iron on neurotransmitter functioning, brain organization, and cellular adaptation to nutrient deficiencies with implications for cognitive and behavioral development. The significance of this work is that it investigates a biologic basis for understanding the behavioral alterations frequently observed in the hundreds of thousands of iron deficient children around the world.