Win-Shwe Tin-Tin, Ohtani Shin, Ushiyama Akira, Kunugita Naoki
Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Department of Environmental Health, National Institute of Public Health, 2-3-6 Minami, Wako City, Saitama 351-0197, Japan.
Int J Environ Res Public Health. 2015 Apr 22;12(4):4406-21. doi: 10.3390/ijerph120404406.
Recently we have reported that intermediate-frequency magnetic field (IF-MF) exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT) for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1), inflammatory mediators (COX2, IL-1 b,TNF-α), and the oxidative stress marker heme-oxygenase (HO)-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes.
最近我们报道,成年雄性小鼠暴露于中频磁场(IF-MF)会短暂改变海马体中记忆功能相关基因的mRNA表达水平。然而,脑发育期间IF-MF暴露对神经生物标志物的影响尚未阐明。在本研究中,我们调查了发育期间IF-MF暴露对3周龄和7周龄雄性小鼠海马体中神经和免疫标志物的影响。怀孕的C57BL/6J小鼠从器官形成期第7天到第17天每天暴露于IF-MF(21kHz,3.8mT)1小时。在青春期,一些暴露于IF-MF的小鼠进一步分为暴露组、恢复组和假暴露组。青春期暴露组从出生后第27天到第48天再次暴露于IF-MF。使用实时RT-PCR方法检测海马体中mRNA的表达,并通过免疫组织化学分析检测小胶质细胞激活情况。与对照组相比,在7周龄小鼠中,IF-MF暴露组小鼠的NR1和NR2B以及转录因子(CaMKIV、CREB1)、炎症介质(COX2、IL-1β、TNF-α)和氧化应激标志物血红素加氧酶(HO)-1的表达水平显著升高,但在3周龄小鼠中未出现这种情况。对照组和其他组之间的小胶质细胞激活情况没有差异。本研究首次提供证据表明,早期暴露于IF-MF会可逆地影响年轻成年小鼠海马体中的NMDA受体、其相关信号通路和炎症介质;这些变化是短暂的,在暴露终止后会恢复,且无组织病理学改变。