Jeong Ye Ji, Kang Ga-Young, Kwon Jong Hwa, Choi Hyung-Do, Pack Jeong-Ki, Kim Nam, Lee Yun-Sil, Lee Hae-June
Division of Radiation Effects, Korea Institute of Radiological & Medical Sciences, Seoul, 139-706, Korea.
Curr Alzheimer Res. 2015;12(5):481-92. doi: 10.2174/156720501205150526114448.
The involvement of radiofrequency electromagnetic fields (RF-EMF) in the neurodegenerative disease, especially Alzheimer's disease (AD), has received wide consideration, however, outcomes from several researches have not shown consistency. In this study, we determined whether RF-EMF influenced AD pathology in vivo using Tg-5xFAD mice as a model of AD-like amyloid β (Aβ) pathology. The transgenic (Tg)-5xFAD and wild type (WT) mice were chronically exposed to RF-EMF for 8 months (1950 MHz, SAR 5W/kg, 2 hrs/day, 5 days/week). Notably, chronic RFEMF exposure significantly reduced not only Aβ plaques, APP, and APP carboxyl-terminal fragments (CTFs) in whole brain including hippocampus and entorhinal cortex but also the ratio of Aβ42 and Aβ40 peptide in the hippocampus of Tg-5xFAD mice. We also found that parenchymal expression of β-amyloid precursor protein cleaving enzyme 1(BACE1) and neuroinflammation were inhibited by RF-EMF exposure in Tg-5xFAD. In addition, RF-EMF was shown to rescue memory impairment in Tg-5xFAD. Moreover, gene profiling from microarray data using hippocampus of WT and Tg- 5xFAD following RF-EMF exposure revealed that 5 genes (Tshz2, Gm12695, St3gal1, Isx and Tll1), which are involved in Aβ, are significantly altered inTg-5xFAD mice, exhibiting different responses to RF-EMF in WT or Tg-5xFAD mice; RF-EMF exposure in WT mice showed similar patterns to control Tg-5xFAD mice, however, RF-EMF exposure in Tg- 5xFAD mice showed opposite expression patterns. These findings indicate that chronic RF-EMF exposure directly affects Aβ pathology in AD but not in normal brain. Therefore, RF-EMF has preventive effects against AD-like pathology in advanced AD mice with a high expression of Aβ, which suggests that RF-EMF can have a beneficial influence on AD.
射频电磁场(RF-EMF)与神经退行性疾病,尤其是阿尔茨海默病(AD)的关联已受到广泛关注,然而,多项研究结果并不一致。在本研究中,我们以Tg-5xFAD小鼠作为类AD淀粉样β(Aβ)病理模型,确定RF-EMF在体内是否会影响AD病理。将转基因(Tg)-5xFAD和野生型(WT)小鼠长期暴露于RF-EMF 8个月(1950 MHz,比吸收率5W/kg,每天2小时,每周5天)。值得注意的是,长期暴露于RF-EMF不仅显著减少了包括海马体和内嗅皮质在内的全脑中的Aβ斑块、淀粉样前体蛋白(APP)和APP羧基末端片段(CTF),还降低了Tg-5xFAD小鼠海马体中Aβ42和Aβ40肽的比例。我们还发现,RF-EMF暴露抑制了Tg-5xFAD中β-淀粉样前体蛋白裂解酶1(BACE1)的实质表达和神经炎症。此外,RF-EMF被证明可挽救Tg-5xFAD中的记忆障碍。此外,对RF-EMF暴露后的WT和Tg-5xFAD小鼠海马体进行微阵列数据分析的基因谱显示,与Aβ相关的5个基因(Tshz2、Gm12695、St3gal1、Isx和Tll1)在Tg-5xFAD小鼠中发生了显著变化,WT或Tg-5xFAD小鼠对RF-EMF表现出不同的反应;WT小鼠暴露于RF-EMF后的模式与对照Tg-5xFAD小鼠相似,然而,Tg-5xFAD小鼠暴露于RF-EMF后表现出相反的表达模式。这些发现表明,长期暴露于RF-EMF直接影响AD中的Aβ病理,但不影响正常大脑。因此,RF-EMF对Aβ高表达的晚期AD小鼠的类AD病理具有预防作用,这表明RF-EMF可能对AD有有益影响。