Effects Of Static Electric Field On Learning And Memory Ability And Gene Expression Of Brain Tissue In Mice

Electric power interconnection is an important part of “The Belt and Road” infrastructure interconnection.It uses ultra-high-voltage power grids as the backbone to construct global energy interconnection,coordinating the exploitation,transmission and utilization of energy resources in the world.As an important technology for constructing global energy interconnection,ultra-high-voltage direct-current(UHVDC)transmission technology has developed rapidly in recent years.China has built the ±800 kV and ±1100 kV UHVDC transmission lines consecutively,whose voltage levels are highest in the world.Accordingly,the strength of static electric field(SEF)near UHVDC transmission lines continuously reaches new heights,which has aroused widely public attention on the potential health effects of SEF.However,so far no international standards exist for limiting exposure to SEF,nor do relevant national standards exist in China except for a power industry standard,which has caused a lot of inconvenience in handling relevant environmental complaints.The World Health Organization,the International Electrotechnical Commission,and the National Radiation Protection Board in the United Kingdom have pointed out that current studies on biological effects of SEF are still lacking.More relevant research,especially animal experimental research,is in a great need in order to conduct the health risk assessment and develop an exposure standard.China is the international technology leader in UHVDC transmission engineering,and should conduct more systematic research for the development of SEF standards.As an important target of electromagnetic fields,nervous system is the research focus of SEF biological effects.Considering the characteristics of electromagnetic environment near UHVDC transmission lines,this study carried out animal experiments both under ±800 kV UHVDC transmission lines and in a high-voltage device in the laboratory.The effects of SEF with different strength and doses on learning and memory ability and relevant biological mechanism were explored by assessing behaviors in Morris water maze(MWM),hippocampal neurotransmitter concentrations,oxidative stress indicators,protein expression levels,Nissl body content,histopathological morphology,and cellular ultrastructure.Moreover,transcriptome deep sequencing was used to explore the influences of SEF exposure on nervous system and its possible mechanism at the molecular biology level.Finally,based on the results of this study and relevant literature,the recommendation on SEF exposure limit was proposed using the international health risk assessment method of electromagnetic fields.The main conclusions are as follows:(1)In the laboratory study,results of MWM behavior test showed that short-term(7 d)SEF exposure with theoretical strength of 80 kV/m(actual value: 55.3±2.7 kV/m)significantly prolonged latency and decreased the number of platform-site crossovers,as well as decreased the percentage of time spent in the target quadrant.After SEF exposure for longer periods(14 d,21 d,35 d and 49 d),all behavioral indicators above showed no significant differences between experimental and control groups.These data indicated that short-term exposure to SEF with theoretical strength of 80 kV/m could lead to the decline in learning and memory ability,and this decline returned to normal level through the self-repair mechanism of organisms after SEF exposure for longer periods.Results of neurotransmitter assay showed that the ratio of glutamate level to gamma-aminobutyric acid level in hippocampus decreased significantly and serotonin level increased significantly after short-term SEF exposure.Results of oxidative stress indices determination showed that after short-term SEF exposure,malondialdehyde content and glutathione peroxidase(GSH-PX)activity in hippocampus increased significantly,and superoxide dismutase(SOD)activity decreased significantly.These data indicated that abnormal neurotransmitter levels and oxidative damage in the hippocampus of mice are important causes of the decline in learning and memory ability.In addition,SEF exposure with theoretical strength of 50 kV/m(actual value: 34.1±1.7 kV/m)and 40 kV/m(actual value: 27.1±1.4 kV/m)had no obvious influences on the performance of mice in MWM test and neurotransmitter levels tested in hippocampus.The experimental results accord with the dose-effect relationship.(2)Results of organisms' self-repair mechanism study showed that mice can repair SEF-induced oxidative damage and decline in learning and memory ability by activating Nrf2-Keap1 signaling pathway.To be specific,80 kV/m SEF exposure could increase Nrf2 protein level in hippocampal cell nucleus,and then raise the expression of downstream antioxidant genes such as GSH-PX1 and SOD2,thereby enhancing the activities of GSH-PX and SOD to resist oxidative damage.After Nrf2-Keap1 signaling pathway was inhibited,the activation of this signaling pathway in hippocampus under SEF exposure could be blocked,and thus,the antioxidant capacity of hippocampus decreased and learning and memory ability could not return to normal level.(3)Results of transcriptome sequencing showed that after exposure to SEF with theoretical strength of 80 kV/m for 49 d,73 differentially expressed genes(DEGs)were identified in brain.Combined with transcriptome sequencing results of other organs under the same exposure condition,it was revealed that the expression of 6 genes was all significantly up-regulated in the brain,liver and testis,which indicated that these 6 genes are sensitive to SEF.KEGG biological pathways analysis showed that the 8 biological pathways,in which DEGs enriched in brain after SEF exposure,mainly involved MHC I-mediated immune response.According to that MHC I-mediated immune response abnormalities involved in pathological processes of Parkinson's disease and multiple sclerosis,the effects of long-term exposure to SEF on these neurological diseases deserve further studies.(4)Results of experiments under actual transmission lines showed that the strength of electric field under actual transmission lines fluctuated greatly with changes of weather.Exposure to 9.20~21.85 kV/m SEF for 35 d caused the decline in learning and memory ability,abnormal content of serotonin in hippocampus and vacuolation of nerve cells ultrastructure.Because the natural environment under actual transmission lines was complex and changeable,it was difficult to meet the suitable keeping conditions of experimental animals.Experimental results were affected not only by SEF exposure,but also by other offset factors such as mosquito bites.Therefore,experimental results under actual transmission lines only can be used as a reference,and experimental results under controlled conditions in the laboratory are prevailing.(5)Results of study on SEF exposure limit showed that 30 kV/m is suitable SEF exposure limit.There is no conclusive evidence to show that 25 kV/m SEF exposure will cause certain health hazards.Thus,it is recommended that when formulating national or international standards,25 kV/m from the existing power industry standard for residential areas should be regarded as a recommended standard,rather than as a mandatory standard.