IRON DEFICIENCY AND DOPAMINE

本研究的主要长期目标是确定 缺铁导致多巴胺代谢功能改变， 对行为的影响本研究将确定 铁与脑组织铁含量的关系 缺乏多巴胺功能障碍和行为改变 此外，委员会认为， 这将在晚期缺铁的背景下进行研究。 哺乳期与断奶后缺铁。 估计有25亿 人类遭受饮食中铁太少的影响;当 这发生在认知的早期发育缺陷期间， 行为发展经常发生。 ”于是，他明白了。 发育时间和神经生物学机制的各个方面似乎 很危险 我们最近在一只断奶后的大鼠中发现， 从大脑中迅速丢失，并可以迅速恢复， 重新进食 铁的损失或恢复并不平等的所有部分， 大脑在消耗和补充。 在纹状体中，有一个 铁损失超过30%， 细胞外多巴胺（DA）。 两者都能迅速用铁正常化 疗法 具体而言，我们建议：1）在体内鉴定改变 在大鼠的关键多巴胺能途径中的多巴胺动力学，2）确定 如果局部脑缺铁改变了 DA在尾壳核突触体中的含量，并确定是否有数量 这些转运蛋白的功能性转运蛋白mRNA发生改变，3） 确定是否有任何种类的DA相关行为（探索其 环境和“焦虑”）受铁状况不良的影响，以及4） 确定铁水平不足的发育时间（断奶前 断奶后）在介导这些效应方面很重要。 的 正在检验的假设是，泌乳后期（PND 10 -21）的ID将 对DA生物学和行为的影响比施加ID时更大 断奶后。 我们还将确定这种影响是否不可逆转 之后再进行铁剂治疗 这些实验的预期结果将 证明DA从神经元间隙的清除是 由于中脑腹侧铁缺乏， 多巴胺转运蛋白的功能 DA的升高 转向导致环境的探索行为减少， 铁缺乏个体的“觉醒”。 我们希望这些研究能够 为未来细胞研究的直接影响奠定基础 局部脑铁对神经递质功能，脑组织， 以及细胞对营养缺乏的适应， 认知和行为发展。 这项工作的意义在于 它研究了生物学基础， 在成千上万的铁中经常观察到的变化 世界各地的缺陷儿童。

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.