Transport of Non-Transferrin Bound Iron to the Brain: Implications for Alzheimer's Disease.
Transport of Non-Transferrin Bound Iron to the Brain: Implications for Alzheimer's Disease.
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DOI：
10.3233/jad-170097
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Singh N
中科院分区：
文献类型：
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作者：
Tripathi AK;Karmakar S;Asthana A;Ashok A;Desai V;Baksi S;Singh N
脑铁和阿尔茨海默病（AD）之间的直接相关性提出了关于非转铁蛋白结合铁（NTBI）的运输的问题，NTBI是一种有毒但研究较少的循环铁池，其可能由于病理性和/或医源性全身铁过载而增加。在这里，我们比较了放射性标记的NTBI（59 Fe-NTBI）和转铁蛋白结合铁（59 Fe-Tf）在小鼠模型中的铁过载在炎症的存在或不存在的分布。在短脉冲之后，大部分59 Fe-NTBI被肝脏吸收，其次是肾脏、胰腺和心脏。值得注意的是，2 h后在脑室系统中检测到59 Fe-NTBI的强信号，24 h后在脑实质中检测到59 Fe-NTBI的强信号。59 Fe-Tf主要蓄积在股骨和脾脏中，并以比59 Fe-NTBI慢得多的速率转运到脑中。在肾脏中，2 h后在皮质中检测到59 Fe-NTBI，24 h后在外髓质中检测到59 Fe-NTBI。大部分来自肾脏的59 Fe-NTBI和59 Fe-Tf被重吸收;尿液中排泄的量可忽略不计。急性炎症从2-24小时增加肾脏和大脑对59 Fe-NTBI的摄取。另一方面，慢性炎症导致铁在肝脏和肾脏中的隔离，减少其向大脑的运输。这些观察结果为NTBI向大脑的转运提供了直接证据，并揭示了炎症和脑铁稳态之间复杂的相互作用。有必要进一步研究以确定由于全身性铁超负荷引起的NTBI一过性增加是否是AD的危险因素。
A direct correlation between brain iron and Alzheimer’s disease (AD) raises questions regarding the transport of non-transferrin-bound iron (NTBI), a toxic but less researched pool of circulating iron that is likely to increase due to pathological and/or iatrogenic systemic iron overload. Here, we compared the distribution of radiolabeled-NTBI (59Fe-NTBI) and transferrin-bound iron (59Fe-Tf) in mouse models of iron overload in the absence or presence of inflammation. Following a short pulse, most of the 59Fe-NTBI was taken up by the liver, followed by the kidney, pancreas, and heart. Notably, a strong signal of 59Fe-NTBI was detected in the brain ventricular system after 2 h, and the brain parenchyma after 24 h. 59Fe-Tf accumulated mainly in the femur and spleen, and was transported to the brain at a much slower rate than 59Fe-NTBI. In the kidney, 59Fe-NTBI was detected in the cortex after 2 h, and outer medulla after 24 hours. Most of the 59Fe-NTBI and 59Fe-Tf from the kidney was reabsorbed; negligible amount was excreted in the urine. Acute inflammation increased the uptake of 59Fe-NTBI by the kidney and brain from 2–24 hours. Chronic inflammation, on the other hand, resulted in sequestration of iron in the liver and kidney, reducing its transport to the brain. These observations provide direct evidence for the transport of NTBI to the brain, and reveal a complex interplay between inflammation and brain iron homeostasis. Further studies are necessary to determine whether transient increase in NTBI due to systemic iron overload is a risk factor for AD.