Bianco Laura E, Unger Erica L, Earley Christopher J, Beard John L
Department of Nutrition Sciences, The Pennsylvania State University, University Park, PA 16892, USA.
Chronobiol Int. 2009 Apr;26(3):447-63. doi: 10.1080/07420520902820905.
Monoamine metabolism in the central nervous system is altered by dietary iron deficiency, with a stronger effect seen during the active than rest span of the circadian cycle. In this report, we examined changes in intracellular and extracellular monoamine levels, synthetic enzymes, transporter and receptor densities, and responses to amphetamine-induced dopamine (DA) efflux in iron-deficient and iron-sufficient mice. Extracellular striatal DA levels were 15-20% higher in all groups during the active dark phase compared to the inactive light phase, with correspondingly lower dopamine transporter (DAT) and higher tyrosine hydroxylase levels. Iron deficiency decreased DAT density by 20% and 28% in the light and dark phases, respectively, and elevated the DOPAC/DA ratio only in the dark, indicating that iron deficiency does interact with the normal diurnal cues for cyclicity. Enhanced DA efflux after amphetamine stimulation indicates no limitation on monoamine synthesis and release and is consistent with altered synaptic efficacy and perhaps recycling of DA in iron deficiency. These experimental findings provide new evidence that brain iron insufficiency does have a differential effect on the DA system at different biological times of the day and night and may be causally related to the phasic motor symptoms observed in Restless Legs Syndrome.
饮食缺铁会改变中枢神经系统中的单胺代谢，在昼夜节律周期的活跃期比休息期产生更强的影响。在本报告中，我们研究了缺铁和铁充足小鼠细胞内和细胞外单胺水平、合成酶、转运体和受体密度的变化，以及对苯丙胺诱导的多巴胺（DA）外流的反应。与非活跃的光照期相比，所有组在活跃的黑暗期纹状体细胞外DA水平高15 - 20%，相应地多巴胺转运体（DAT）水平较低，酪氨酸羟化酶水平较高。缺铁在光照期和黑暗期分别使DAT密度降低20%和28%，并且仅在黑暗期提高了DOPAC/DA比值，表明缺铁确实与正常的昼夜周期性线索相互作用。苯丙胺刺激后增强的DA外流表明单胺合成和释放没有限制，并且与缺铁时突触效能改变以及DA的可能再循环一致。这些实验结果提供了新的证据，即脑铁不足在白天和夜晚的不同生物学时间对DA系统确实有不同影响，并且可能与不宁腿综合征中观察到的阶段性运动症状有因果关系。
