Youdim M B H
Eve Topf and USA National Parkinson Foundation, Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, Israel.
Neurotox Res. 2008 Aug;14(1):45-56. doi: 10.1007/BF03033574.
While iron deficiency is not perceived as a life threatening disorder, it is the most prevalent nutritional abnormality in the world, and a better understanding of modes and sites of action, can help devise better treatment programs for those who suffer from it. Nowhere is this more important than in infants and children that make up the bulk of iron deficiency in society. Although the effects of iron deficiency have been extensively studied in systemic organs, until very recently little attention was paid to its effects on brain function. The studies of Oski at Johns Hopkin Medical School in 1974, demonstrating the impairment of learning in young school children with iron deficiency, prompted us to study its relevance to brain biochemistry and function in an animal model of iron deficiency. Indeed, rats made iron deficient have lowered brain iron and impaired behaviours including learning. This can become irreversible especially in newborns, even after long-term iron supplementation. We have shown that in this condition it is the brain striatal dopaminergic-opiate system which becomes defective, resulting in alterations in circadian behaviours, cognitive impairment and neurochemical changes closely associated with them. More recently we have extended these studies and have established that cognitive impairment may be closely associated with neuroanatomical damage and zinc metabolism in the hippocampus due to iron deficiency, and which may result from abnormal cholinergic function. The hippocampus is the focus of many studies today, since this brain structure has high zinc concentration and is highly involved in many forms of cognitive deficits as a consequence of cholinergic deficiency and has achieved prominence because of dementia in ageing and Alzheimer's disease. Thus, it is now apparent that cognitive impairment may not be attributed to a single neurotransmitter, but rather, alterations and interactions of several systems in different brain regions. In animal models of iron deficiency it is apparent that dopaminergic interaction with the opiate system and cholinergic neurotransmission may be defective.
虽然缺铁不被视为一种危及生命的疾病，但它却是世界上最普遍的营养异常情况，更好地了解其作用方式和作用部位，有助于为缺铁患者设计出更好的治疗方案。这一点在构成社会缺铁人群主体的婴幼儿和儿童中尤为重要。尽管缺铁对全身各器官的影响已得到广泛研究，但直到最近，人们才开始关注其对脑功能的影响。1974年约翰·霍普金斯医学院的奥尔斯基进行的研究表明，缺铁的学龄儿童学习能力受损，这促使我们在缺铁动物模型中研究其与脑生物化学及功能的相关性。事实上，缺铁的大鼠脑铁含量降低，行为受损，包括学习能力下降。这种情况尤其在新生儿中可能会变得不可逆转，即使长期补充铁之后也是如此。我们已经表明，在这种情况下，脑纹状体多巴胺能 - 阿片系统会出现缺陷，导致昼夜节律行为改变、认知障碍以及与之密切相关的神经化学变化。最近，我们扩展了这些研究，并确定认知障碍可能与缺铁导致的海马体神经解剖损伤和锌代谢密切相关，而这可能是由于胆碱能功能异常所致。海马体是当今许多研究的焦点，因为这个脑结构锌浓度高，并且由于胆碱能缺乏而高度参与多种形式的认知缺陷，还因为在衰老和阿尔茨海默病中的痴呆现象而备受关注。因此，现在很明显，认知障碍可能并非归因于单一神经递质，而是不同脑区中多个系统的改变和相互作用。在缺铁动物模型中，多巴胺能与阿片系统的相互作用以及胆碱能神经传递明显存在缺陷。
