Supplementary Material for: New view on the impact of the low-frequency electromagnetic field (50 Hz) on stress responses – hormesis effect

Introduction: Low-frequency electromagnetic field (50 Hz) (EMF) can modify crucial neuronal processes. Existing data indicate that exposure to EMF may represent a mild stressor and contribute to disturbances of hypothalamic-pituitary-adrenal (HPA) axis. The important regulatory pathways controlling HPA axis activity include two types of corticosteroid receptors: mineralocorticoid (MR) and glucocorticoid (GR) receptors. There are particularly abundant in the hippocampus, a key locus of HPA axis feedback control. The research aimed at determining whether 1) EMF exhibits hormesis, it means bidirectional action depending on EMF intensity (1 or 7 mT), and 2) repeated EMF exposure changes stress response to subsequent stress factors. Methods: The exposure (7-day, 1h/day) of adult rats to EMF (1 mT and 7 mT) was repeated 3 times. HPA axis hormones and their receptors were analysed after each following exposure. Moreover, the impact of EMF exposure on hormonal and behavioural responses to subsequent stress factor - open-field test was evaluated. Results/Discussion: Our data suggest that exposure to EMF can establish a new “set-point” for HPA axis activity. The direction and dynamics of this process depend on the intensity of EMF and the number of exposures. EMF of 1 mT induced an adaptive stress response, but 7 mT EMF caused sensitization. Consequently, EMF changed the vulnerability of the organism to a subsequent stress factor. We have also shown the increase of MR mRNA abundance in hippocampus of 1 mT EMF exposed rats, which can represent the possible neuroprotective response and suggest therapeutic properties of electromagnetic fields.引言：50 Hz低频电磁场（electromagnetic field, EMF）可调控关键神经元生理过程。现有研究数据显示，电磁场暴露可作为一种轻度应激源，参与下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal, HPA）轴的功能紊乱进程。调控HPA轴活性的重要通路包含两类糖皮质激素受体：盐皮质激素受体（mineralocorticoid, MR）与糖皮质激素受体（glucocorticoid, GR），二者在海马体中表达尤为丰富，而海马体正是HPA轴反馈调控的关键位点。本研究旨在明确两个科学问题：1）电磁场是否存在毒物兴奋效应（hormesis），即其生物学效应取决于电磁场强度（1 mT或7 mT）；2）反复电磁场暴露是否会改变机体对后续应激源的应激反应。 方法：将成年大鼠暴露于1 mT与7 mT的电磁场中，每次暴露时长1小时，每日1次，连续7天，该暴露流程重复3次。在每次暴露结束后，分别检测HPA轴相关激素及其受体的表达水平。此外，本研究还评估了电磁场暴露对后续应激源——旷场实验（open-field test）的激素与行为学反应的影响。 结果与讨论：本研究数据显示，电磁场暴露可使HPA轴活性建立新的“设定点”，该过程的方向与动态变化取决于电磁场强度与暴露次数。1 mT电磁场可诱导适应性应激反应，而7 mT电磁场则会引发应激敏化。相应地，电磁场暴露会改变机体对后续应激源的易感性。本研究还发现，1 mT电磁场暴露大鼠的海马体中MR mRNA表达丰度升高，这可能代表一种潜在的神经保护应答，提示电磁场具备潜在的治疗应用价值。