50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响

张彦文; 马秦龙; 高鹏; 邓平; 皮会丰; 张蕾; 陈纯海; 何旻蒂; 卢永辉; 谢佳; 田丽; 陈梦妍; 余争平

doi:10.16016/j.2097-0927.202206091

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50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响

神经科学 | 更新时间：2026-01-09

- 50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响
- Effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice
- 陆军军医大学学报 2023年45卷第4期页码：277-290
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)军事预防医学系军队劳动卫生学教研室，电磁辐射医学防护教育部重点实验室
- 作者简介：
  
  [张彦文，E-mail: zhangyw20022002@aliyun.comZHANG Yanwen, E-mail: zhangyw20022002@aliyun.com
- 基金信息：
  
  国家自然科学基金面上项目(31770906)
- DOI：10.16016/j.2097-0927.202206091
  中图分类号： R-332;R322.81;R594.8
- 收稿：2022-06-15，
  
  修回：2022-09-23，
  
  纸质出版：2023-02-28
- 稿件说明：
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张彦文, 马秦龙, 高鹏, 等. 50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响[J]. 陆军军医大学学报, 2023,45(4):277-290.

Yanwen ZHANG, Qinlong MA, Peng GAO, et al. Effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice[J]. Journal of Army Medical University, 2023, 45(4): 277-290.
张彦文, 马秦龙, 高鹏, 等. 50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响[J]. 陆军军医大学学报, 2023,45(4):277-290. DOI： 10.16016/j.2097-0927.202206091.

Yanwen ZHANG, Qinlong MA, Peng GAO, et al. Effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice[J]. Journal of Army Medical University, 2023, 45(4): 277-290. DOI： 10.16016/j.2097-0927.202206091.

摘要

目的

探究50 Hz磁场暴露对APP/PS1双转基因小鼠大脑皮层组织代谢的影响。

方法

将12只APP/PS1双转基因12周龄雄性小鼠随机分为对照组(C组)和50 Hz磁场暴露组(MF组)，每组6只。磁场暴露组小鼠暴露在1.0 mT 50 Hz磁场中，2 h/d，持续21 d；对照组小鼠除无磁场暴露外，其余条件与磁场暴露组相同。暴露结束后按标准方法取小鼠大脑皮层组织，进行高分辨非靶代谢组学检测，包括样品代谢物提取、样品LC-MS/MS质谱分析、代谢物定性定量、数据分析等。

结果

50 Hz磁场暴露对APP/PS1双转基因小鼠的发育无明显影响。本次高分辨非靶代谢组学检测共鉴定出1 068种代谢物。依据变异倍数分析(FC

1.5或FC

0.67倍，

0.05)，50 Hz磁场暴露后小鼠皮层组织共定性出22种差异代谢物，其中11-酮-β-乳香酸增加最明显(FC=80.68)，5-氨基酮戊酸降低最明显(FC=0.34)。依据OPLS-DA (VIP

1，

0.05)，共筛选30种差异代

谢物，其中VIP位居前3位的是2-油酰-1-软脂酰-sn-甘油-3-磷酸胆碱(VIP=19.76，FC=0.52)、去氢抗坏血酸(VIP=12.71，FC=0.72)、肌苷(VIP=10.64，FC=1.05)。差异代谢物层次聚类分析、相关性和KEGG通路分析显示，这些差异代谢物可能参与了16条KEGG通路，其中差异代谢物L-天冬氨酸可参与其中的13条通路、L-丙氨酸可参与其中的7条通路、乙酰胆碱可参与其中的3条通路。

结论

50 Hz磁场暴露可能对APP/PS1双转基因小鼠的氨基酸代谢、蛋白转运、辅酶A和氨酰tRNA生物合成、肌动蛋白细胞骨架调节、神经细胞配体-受体的相互作用等方面产生一定影响。

Abstract

Objective

To study the effects of 50 Hz magnetic field exposure on metabolism of cerebral cortex in APP/PS1 transgenic mice.

Methods

Twelve 12-week-old male APP/PS1 double transgenic mice were randomly divided into the control group (C group) and the 50 Hz magnetic field exposure group (MF group) (

=6). The mice in the MF group were exposed to 1.0 mT 50 Hz magnetic field 2 h/d for 3 weeks (21 d). The mice in the sham exposure group had the same conditions as those in the MF group

except for no magnetic field exposure. After exposure

the cerebral cortex tissues of mice were taken according to the standard method for high-resolution untargeted metabonomics tests

including sample metabolite extraction

sample LC-MS/MS mass spectrometry analysis

metabolite qualitative and quantitative analysis and data analysis.

Results

The growth of APP/PS1 double transgenic mice were not affected after 50 Hz magnetic field exposure. The high-resolution untargeted metabonomics showed 1 068 metabolites were identified. Based on fold change analysis (FC

1.5 or FC

0.67

0.05)

22 significant changed metabolites were identified in cerebral cortex of mice after 50 Hz magnetic field exposure

and 11-keto-beta-boswellic acid was the most increased metabolite (FC=80.68)

and 5-aminolevulinic acid was the most decreased metabolite (FC=0.34). Based on the variable importance in the projection (VIP) value of each variable in the orthogonal partial least-squares discriminant analysis (OPLS-DA) mod

el (VIP

0.05)

30 identified significant changed metabolites were screened in cerebral cortex of mice after 50 Hz magnetic field exposure. And the top 3 significant changed metabolites in VIP value were 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (VIP=19.76

FC=0.52)

dehydroascorbic acid (VIP=12.71

FC=0.72) and inosine (VIP=10.64

FC=1.05). The analyses of hierarchical clustering

correlation and Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the 30 VIP significant changed metabolites may be involved in 16 KEGG pathways. L-aspartic acid

L-alanine and acetylcholine may be involved in 13

7 and 3 pathways of the 16 KEGG pathways respectively.

Conclusion

The amino acid metabolism

ATP-binding cassette transporters

CoA and aminoacyl-tRNA biosynthesis

regulation of actin cytoskeleton and neuroactive ligand-receptor interaction may be impacted in cerebral cortex of APP/PS1 transgenic mice by 50 Hz magnetic field exposure.

关键词

Keywords

references

WORLD HEALTH ORGANIZATION. Global status report on the public health response to dementia. https://www.who.int/health-topics/dementia https://www.who.int/health-topics/dementia

QIU C X, FRATIGLIONI L, KARP A, et al . Occupational exposure to electromagnetic fields and risk of alzheimer's disease[J ] . Epidemiology, 2004, 15(6): 687-694. DOI: 10.1097/01.ede.0000142147.49297.9d.

DEL GIUDICE E, FACCHINETTI F, NOFRATE V, et al . Fifty Hertz electromagnetic field exposure stimulates secretion of beta-amyloid peptide in cultured h uman neuroglioma[J ] . Neurosci Lett, 2007, 418(1): 9-12. DOI: 10.1016/j.neulet.2007.02.057.

DENG Y X, ZHANG Y W, JIA S J, et al . Effects of aluminum and extremely low frequency electromagnetic radiation on oxidative stress and memory in brain of mice[J ] . Biol Trace Elem Res, 2013, 156(1/2/3): 243-252. DOI: 10.1007/s12011-013-9847-9.

DAVANIPOUR Z, TSENG C C, LEE P J, et al . Severe cogni tive dysfunction and occupational extremely low frequency magnetic field exposure among elderly mexican americans[J ] . Br J Med Med Res, 2014, 4(8): 1641-1662. DOI: 10.9734/bjmmr/2014/7317.

HU Y, LAI J S, WAN B Q, et al . Long-term exposure to elf-mf ameliorates cognitive deficits and attenuates tau hyperphosphorylation in 3xtg AD mice[J ] . Neurotoxicology, 2016, 53: 290-300. DOI: 10.1016/J.Neuro.2016.02.012.

ZUO H Y, LIU X, LI Y, et al . The mitochondria/caspase-dependent apoptotic pathway plays A role in the positive effects of a power frequency electromagnetic field on alzheimer's disease neuronal model[J ] . J Chem Neuroanat, 2020, 109: 101857. DOI: 10.1016/j.jchemneu.2020.101857.

ZUO H Y, LIU X, WANG D W, et al . RKIP-mediated NF-κB signaling is involved in elf-mf-mediated improvement in AD rat[J ] . Int J Med Sci, 2018, 15(14): 1658-1666. DOI: 10.7150/Ijms.28411.

HOLCOMB L, GORDON M N, MCGOWAN E, et al . Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes[J ] . Nat Med, 1998, 4(1): 97-100. DOI: 10.1038/nm0198-097.

CHANG K L, WONG L R, PEE H N, et al . Reverting metabolic dysfunction in cortex and cerebellum of APP/PS1 mice, a model for Alzheimer's disease by pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist[J ] . Mol Neurobiol, 2019, 56(11): 7267-7283. DOI: 10.1007/s12035-019-1586-2.

PODDAR M K, BANERJEE S, CHAKRABORTY A, et al . Metabolic disorder in Alzheimer's disease[J ] . Metab Brain Dis, 2021, 36(5): 781-813. DOI: 10.1007/s11011-021-00673-Z.

KELLAR D, CRAFT S. Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches[J]. Lancet Neurol, 2020, 19(9): 758-766. DOI: 10.1016/s1474-4422(20)30231-3.

ZHU T B, ZHANG Z, LUO P, et al . Lipid metabolism in Alzheimer's disease[J ] . Brain Res Bull, 2019, 144(2): 68-74. DOI: 10.1016/j.brainresbull.2018.11.012.

YIN F, SANCHETI H, PATIL I, et al . Energy metabolism and inflammation in brain aging and Alzheimer's disease[J ] . Free Radic Biol Med, 2016, 100: 108-122. DOI: 10.1016/j.freeradbiomed.2016.04.200.

MARTIÑÓN-GUTIÉRREZ G, LUNA-CASTRO M, HERN-ÁNDEZ-MUÑOZ R. Role of insulin/glucagon ratio and cell redox state in the hyperglycaemia induced by exposure to a 60-Hz magnetic field in rats[J]. Sci Rep, 2021, 11(1): 11666. DOi: 10.1038/s41598-021-91228-w.

SUN Y Y, SHI Z H, WANG Y H, et al . Coupling of oxidative stress responses to tricarboxylic acid cycle and prostaglandin E2 alterations in Caenorhabditis elegans under extremely low-frequency electromagnetic field[J ] . Int J Radiat Biol, 2018, 94(12): 1159-1166. DOI: 10.1080/09553002.2019.1524943..

SUN Y Y, HUANG X M, WANG Y H, et al . Lipidomic alteration and stress-defense mechanism of soil nematode caenorhabditis elegans in response to extremely low-frequency electromagnetic field exposure[J ] . Ecotoxicol Environ Saf, 2019, 170: 611-619. DOI: 10.1016/j.ecoenv.2018.11.137.

JIA J P, JIA J M, ZHOU W D, et al . Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia[J ] . Chin Med J (Engl), 2004, 117(8): 1161-1164.

IKARASHI Y, HARIGAYA Y, TOMIDOKORO Y, et al . Decreased level of brain acetylcholine and memory disturbance in APP SW mice[J ] . Neurobiol Aging, 2004, 25(4): 483-490. DOI: 10.1016/S0197-4580(03)00122-2.

AFRASIABI A, RIAZI G H, ABBASI S, et al . Synaptosomal acetylcholinesterase activity variation pattern in the presence of electromagnetic fields[J ] . Int J Biol Macromol, 2014, 65: 8-15. DOI: 10.1016/j.ijbiomac.2014.01.006.

RAVERA S, BIANCO B, CUGNOLI C, et al . Sinusoidal ELF magnetic fields affect acetylcholinesterase activity in cerebellum synaptosomal membranes[J ] . Bioelectromagnetics, 2010, 31(4): 270-276. DOI: 10.1002/bem.20563.

ZHANG C, RODRIGUEZ C, SPAULDING J, et al . Age-dependent and tissue-related glutathione redox status in a mouse model of Alzheimer's disease[J ] . J Alzheimers Dis, 2012, 28(3): 655-666. DOI: 10.3233/jad-2011- 111244.

MANIKONDA P K, RAJENDRA P, DEVENDRANATH D, et al . Extremely low frequency magnetic fields induce oxidative stress in rat brain[J ] . Gen Physiol Biophys, 2014, 33(1): 81-90. DOI: 10.4149/GPB_2013059.

LIU Y Y, LIU Z Y, WEI M Y, et al . Pharmacodynamic and urinary metabolomics studies on the mechanism of schisandra polysaccharide in the treatment of Alzheimer's disease[J ] . Food Funct, 2019, 10(1): 432-447. DOI: 10.1039/c8fo02067a.

KORI M, AYDN B, UNAL S, et al . Metabolic biomarkers and neurodegeneration: a pathway enrichment analysis of Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis[J ] . OMICS, 2016, 20(11): 645-661. DOI: 10.1089/omi.2016.0106.

FONTEH A N, HARRINGTON R J, TSAI A, et al . Free amino acid and dipeptide changes in the body fluids from Alzheimer's disease subjects[J ] . Amino Acids, 2007, 32(2): 213-224. DOI: 10.1007/S00726-006-0409-8.

ZECCA L, FERRARIO P, MARGONATO V, et al . Neurotransmitter amino acid variations in striatum of rats exposed to 50 Hz electric fields[J ] . Biochim Biophys Acta, 1991, 1075(1): 1-5. DOI: 10.1016/0304-4165(91)90066-P.

CHUNG Y H, LEE Y J, LEE H S, et al . Extremely low frequ-ency magnetic field modulates the level of neurotransmitters[J ] . Korean J Physiol Pharmacol, 2015, 19(1): 15-20. DOI: 10.4196/kjpp.2015.19.1.15.

侯文韬, 王亮, 徐达, 等. ABC转运蛋白与人类疾病[J]. 中国科学技术大学学报, 2018, 48(10): 853-861.

HOU W T, WANG L, XU D, et al . ABC transporters and human diseases[J ] . J Univ Sci Technol China, 2018, 48(10): 853-861.

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