Journal of Biosciences

, Volume 43, Issue 2, pp 263–276 | Cite as

Electromagnetic radiation 2450 MHz exposure causes cognition deficit with mitochondrial dysfunction and activation of intrinsic pathway of apoptosis in rats

  • Sukesh Kumar Gupta
  • Manoj Kumar Mesharam
  • Sairam KrishnamurthyEmail author


Electromagnetic radiation (EMR) can induce or modulate several neurobehavioral disorders. Duration and frequency of exposure of EMR is critical to develop cognitive disorders. Even though EMR-2450 is widely used, its effects on cognition in relation to mitochondrial function and apoptosis would provide better understanding of its pathophysiological effects. Therefore, a comparative study of different frequencies of EMR exposure would give valuable information on effects of discrete frequencies of EMR on cognition. Male rats were exposed to EMR (900, 1800 and 2450 MHz) every day for 1 h for 28 consecutive days. The cognitive behavior in terms of novel arm entries in Y-maze paradigm was evaluated every week after 1 h to last EMR exposure. Animals exposed to EMR-2450 MHz exhibited significant cognitive deficits. EMR-2450 MHz caused loss of mitochondrial function and integrity, an increase in amyloid beta expression. There was release of cytochrome-c and activation of apoptotic factors such as caspase-9 and -3 in the hippocampus. Further, there was decrease in levels of acetylcholine, and increase in activity of acetyl cholinesterase, indicating impairment of cholinergic system. Therefore, exposure of EMR-2450 in rats caused cognitive deficit with related pathophysiological changes in mitochondrial and cholinergic function, and amyloidogenesis.


Apoptosis cognition electromagnetic radiation – 900, 1800, 2450 MHz hippocampus mitochondria 



SKG is thankful to Indian Institute of Technology–Banaras Hindu University (IIT-BHU), Varanasi, India, for the fellowship as teaching assistant. All animal experiments were carried out according to the principles stated in guidelines of laboratory animal care (National Research Council US Committee for the Update of the Guide for the Care and Use of Laboratory Animals 2011 guidelines). All the experimental methods were approved by the Institutional animal ethical committee, Banaras Hindu University (Approval No.: Dean/2015/CAEC/1414).


  1. Afrasiabi A, Riazi GH, Abbasi S, Dadras A, Ghalandari B, Seidkhani H, Modaresi SM, Masoudian N, Amani A and Ahmadian S 2014 Synaptosomal acetylcholinesterase activity variation pattern in the presence of electromagnetic fields. Int. J. Biol. Macromol. 65 8–15CrossRefPubMedGoogle Scholar
  2. Balanis CA 1997 Antenna theory, analysis and design 2nd edition (Wiley)Google Scholar
  3. Beers Jr RF and Sizer IW 1952 A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 195 133–140PubMedGoogle Scholar
  4. Borutaite V, Toleikis A and Brown GC, 2013 In the eye of the storm: mitochondrial damage during heart and brain ischaemia. FEBS J. 280 4999–5014CrossRefPubMedGoogle Scholar
  5. Bradford MM 1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72 248–254CrossRefPubMedGoogle Scholar
  6. Brahima S 2015 Assignment and use of radio spectrum-policy guideline and economic aspects. Columbia University, USAGoogle Scholar
  7. Cai ZL, Wang CY, Jiang ZJ, Li HH, Liu WX, Gong LW, Xiao P and Li CH 2013 Effects of cordycepin on Y-maze learning task in mice. Eur. J. Pharmacol. 714 249–253CrossRefPubMedGoogle Scholar
  8. Chen HW, He XH, Yuan R, Wei BJ, Chen Z, Dong JX and Wang J, 2016 Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo. Fitoterapia 110 142–149CrossRefPubMedGoogle Scholar
  9. Chen JX and Yan SS, 2010 Role of mitochondrial amyloid-β in Alzheimer’s disease. J. Alzheimer Dis. 20 569–578.CrossRefGoogle Scholar
  10. Choi Y and Choi Y 2016 Effects of electromagnetic radiation from smartphones on learning ability and hippocampal progenitor cell proliferation in mice. Osong Public Health Res. Perspect. 7 12–17CrossRefPubMedGoogle Scholar
  11. Conrad CD, Galea LA, Kuroda Y and McEwen BS 1997 Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment. Behav. Neurosci. 110 1321–1334CrossRefGoogle Scholar
  12. Diana A, Simić G, Sinforiani E, Orrù N, Pichiri G and Bono G 2008 Mitochondria morphology and DNA content upon sub lethal exposure to beta amyloid (1–42) peptide. Collegium Antropol. 32 51–58Google Scholar
  13. Dogan M, Turtay M, Oquzturk H, Samdanie E, Turkoz Y, Tasdemir S, Alkan A and Bakir S 2012 Effects of electromagnetic radiation produced by 3G mobile phones on rat brain: magnetic resonance spectroscopy, biochemical and histopathological evaluation. Hum. Exp. Toxicol. 31 557–564CrossRefPubMedGoogle Scholar
  14. Dubreuil D, Jay T and Edeline JM 2003 Head-only exposure to GSM 900-MHz electromagnetic fields does not alter rat’s memory in spatial and non-spatial tasks. Behav. Brain Res. 145 51–61CrossRefPubMedGoogle Scholar
  15. Fiske CH and Subbarao Y 1925 The colorimetric determination of phosphorus. J. Biol. Chem. 66 375–400Google Scholar
  16. Fontolliet G 1996 Traite d’Electricite, Vol. XVIII: Systems de telecommunications (Presses Polytechniques et Universitaires Romandes)Google Scholar
  17. Fu Z, Yang J, Wei Y and Li J 2016 Effects of piceatannol and pterostilbene against β-amyloid-induced apoptosis on the PI3K/Akt/Bad signaling pathway in PC12 cells. Food Funct. 7 1014–1023CrossRefPubMedGoogle Scholar
  18. Gandhi OP 1990 Biological effects and medical applications of electromagnetic energy (Prentice Hall, Upper Saddle River)Google Scholar
  19. Glenner GG and Wong CW 1984 Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120 885–890CrossRefPubMedGoogle Scholar
  20. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS and Tannenbaum SR 1982 Analysis of nitrate, nitrite, and nitrate in biological fluids. Anal. Biochem. 126 131–138CrossRefPubMedGoogle Scholar
  21. Griffiths DE and Houghton RL 1974 Studies on energy linked reactions, modified mitochondrial ATPase of oligomycin-resistant mutants of Saccharomyces cerevisiae. Eur. J. Biochem. 46 157–167CrossRefPubMedGoogle Scholar
  22. Grill JD and Cummings JL 2010 Novel targets for Alzheimer’s disease treatment. Expert Rev. Neurother. 10 711–728CrossRefPubMedPubMedCentralGoogle Scholar
  23. Guo C, Li S, Chen X and Zhang D 2013 Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res. 8 2003–2014PubMedPubMedCentralGoogle Scholar
  24. Hao YH, Zhao L and Peng RY 2015 Effects of microwave radiation on brain energy metabolism and related mechanisms. Military Med. Res. 2 4CrossRefGoogle Scholar
  25. Hidisoglu E, Gok DK, Akpinar D, Uysal F, Akkoyunlu G, Ozen S, Agar A and Yargicoglu P 2016 2100 MHz electromagnetic fields have different effects on visual evoked potentials and oxidant/antioxidant status depending on exposure duration. Brain Res. 1635 1–11CrossRefPubMedGoogle Scholar
  26. Himmelheber AM, Sarter M and Bruno JP 2000 Increases in cortical acetylcholine release during sustained attention performance in rats. Brain Res. 9 313–325Google Scholar
  27. Holloway CL, Mckenna PM, Dalke RA, Perala RA and Devor CL 2002 Time- domain modeling characterization, measurements of semi-anechoic and anechoic electromagnetic test chambers. IEEE Trans. Electromagn. Compat. 44 1Google Scholar
  28. Hossmann KA and Hermann DM 2003 Effects of electromagnetic radiation of mobile phones on the central nervous system. Bioelectromagneticx 24 49–62CrossRefGoogle Scholar
  29. Huang SG 2002 Development of a high throughput screening assay for mitochondrial membrane potential in living cells. J. Biomol. Screen. 7 383–389CrossRefPubMedGoogle Scholar
  30. Huber R, Treyer V, Schuderer J, Berthold T, Buck A, Kuster N, Landolt HP and Achermann P 2005 Exposure to pulse-modulated radio frequency electromagnetic fields affects regional cerebral blood flow. Eur. J. Neurosci. 21 1000–1006CrossRefPubMedGoogle Scholar
  31. Jänicke RU, Ng P, Sprengart ML and Porter AG 1998 Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. J. Biol. Chem. 273 15540–15545CrossRefPubMedGoogle Scholar
  32. Jiang DP, Li J, Zhang J, Xu SL, Kuang F, Lang HY, Wang YF, An GZ, Li JH and Guo GZ 2013 Electromagnetic pulse exposure induces over expression of beta amyloid protein in rats. Arch. Med. Res. 44 178–184CrossRefPubMedGoogle Scholar
  33. Joshi R, Garabadu D, Teja GR and Krishnamurthy S 2014 Silibinin ameliorates LPS-induced memory deficits in experimental animals. Neurobiol. Learn Mem. 16 117–131CrossRefGoogle Scholar
  34. Kakkar P, Das B and Viswanathan PN 1984 A modified spectrophotometric assay of superoxide dismutase. Indian J. Biochem. Biophys. 21 130–132PubMedGoogle Scholar
  35. Kamboj SS, Kumar V, Kamboj A and Sandhir R, 2008 Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure. Cell. Mol. Neurobiol. 28 961–969CrossRefPubMedGoogle Scholar
  36. Krishnamurthy S, Garabadu D and Joy KP 2013 Risperidone ameliorates post-traumatic stress disorder-like symptoms in modified stress re-stress model. Neuropharmacology 75 62–77CrossRefPubMedGoogle Scholar
  37. Lai H, Horita A, Chon CK and Gey W 1987 Low level microwave irradiations affect central cholinergic activity in the rat. J. Neurochem. 48 440–445CrossRefGoogle Scholar
  38. Langrange X, Godlewski P, Tabbane S and Reseaux 1999 GSM-DCS.4mem edition. Hermes Science Publications Section 6 2.1.2Google Scholar
  39. Levin ED 2015 Learning about cognition risk with the radial-arm maze in the developmental neurotoxicology battery. Neurotoxicol. Teratol. 52 88–92CrossRefGoogle Scholar
  40. Li Y, Shi C, Lu G, Xu Q, and Liu S 2012 Effects of electromagnetic radiation on spatial memory and synapses in rat hippocampal CA1. Neural Regen. Res. 7 1248–1255PubMedPubMedCentralGoogle Scholar
  41. Lowry OH, Rosenborough NJ, Farr AL and Randall RJ 1951 Protein measurement with folin phenol reagent. J. Biol. Chem. 193 265–275PubMedGoogle Scholar
  42. Lykhmus O, Gergalova G, Koval L, Zhmak M and Komisarenko SM, 2014 Mitochondria express several nicotinic acetylcholine receptor subtypes to control various pathways of apoptosis induction. Int. J. Biochem. Cell Biol. 53 246–252CrossRefPubMedGoogle Scholar
  43. Man YG, Zhou RG and Zhao B 2015 Efficacy of rutin in inhibiting neuronal apoptosis and cognitive disturbances in sevoflurane or propofol exposed neonatal mice. Int. J. Clin. Exp. Med. 8 14397–14340Google Scholar
  44. McEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos AM and McKittrick C 1997 Prevention of stress-induced morphological and cognitive consequences. Eur. Neurophycopharmacol. 7 323–328CrossRefGoogle Scholar
  45. Muthuraju S, Maiti P, Solanki P, Sharma AK, Amitabh S, Prasad D and Ilavazhagan G 2009 Acetylcholinesterase inhibitors enhance cognitive functions in rats following hypobaric hypoxia. Behav. Brain Res. 203 1–14CrossRefPubMedGoogle Scholar
  46. Narayanan SN, Kumar RS, Karun KM, Nayak SB and Bhat PG 2015 Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation. Metab. Brain Dis. 30 1193–1206CrossRefPubMedGoogle Scholar
  47. Naziroglu M, Celik O, Ozgul C, Cig B, Dogan S, Bal R, Gumral N, Rodriguez AB and Pariente JA 2012 Melatonin modulates wireless (2.45 GHz)-induced oxidative injury through TRPM2 and voltage gated Ca (2+) channels in brain and dorsal root ganglion in rat. Physiol. Behav. 105 683–669CrossRefGoogle Scholar
  48. Neve RL, Dawes LR, Yankner BA, Benowitz LL, Rodriguez W and Higgins GA 1990 Genetics and biology of the Alzheimer amyloid precursor. Prog. Brain Res. 86 257–267CrossRefPubMedGoogle Scholar
  49. Ohkawa H, Ohishi N and Yagi K 1979 Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95 351–358CrossRefPubMedGoogle Scholar
  50. Ott M, Gogvadze V, Orrenius S and Zhivotovsky B 2007 Mitochondria, oxidative stress and cell death. Apoptosis 12 913–922CrossRefPubMedGoogle Scholar
  51. Paxinos G and Watson C 1986 The rat brain in stereotaxic coordinates (Academic Press, Cambridge)Google Scholar
  52. Pedersen PL, Greenawalt JW, Reynafarje B, Hullihen J, Decker GL, Soper JW and Bustamente E 1978 Preparation and characterization of mitochondria and sub mitochondrial particles of rat liver-derived tissues. Methods Cell Biol. 20 411–481CrossRefPubMedGoogle Scholar
  53. Pinho CM, Teixeira PF and Glaser E 2014 Mitochondrial import and degradation of amyloid-β peptide. Biochim. Biophys. Acta 1837 1069–1074CrossRefPubMedGoogle Scholar
  54. Pochynyuk OM, Zaika OL and Lukyanetz EA 2002 Role of mitochondria in the generation of acetylcholine-induced calcium transients in rat chromaffin cells. Neurophysiology 34 204–206CrossRefGoogle Scholar
  55. Poimenova A, Markaki E, Rahiotis C and Kitraki E 2010 Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A. Neuroscience 19 741–749CrossRefGoogle Scholar
  56. Pozueta, J, Lefort R and Shelanski ML 2013 Synaptic changes in Alzheimer’s disease and its models. Neuroscience 251 51–65CrossRefPubMedGoogle Scholar
  57. Repacholi MH, Basten A, Gebski V, Noonan D, Finnie J and Harris AW 1997 Lymphomas in Eµ-Pim 1 transgenic mice exposed to pulsed 900 MHz electromagnetic fields. Rad. Res. 147 631–640CrossRefGoogle Scholar
  58. Sally LO and Margaret AJ 1989 Methods of microphotometric assay of succinate dehydrogenase and cytochrome-C oxidase activities for use on human skeletal muscle. Histochem. J. 21 545–555CrossRefGoogle Scholar
  59. Samaiya PK, Narayan G, Kumar A and Krishnamurthy S 2016 Neonatal anoxia leads to time dependent progression of mitochondrial linked apoptosis in rat cortex and associated long term sensorimotor deficits. Int. J. Dev. Neurosci. 52 55–65CrossRefPubMedGoogle Scholar
  60. Santini E and Turner KL 2015 Mitochondrial superoxide contributes to hippocampal synaptic dysfunction and memory deficits in Angelman syndrome model mice. J. Neurosci. 35 16213–16220CrossRefPubMedPubMedCentralGoogle Scholar
  61. Shapiro BL, Feigal RJ and Lam FH 1979 Mitochondrial NADH dehydrogenase in cystic fibrosis. Proc. Natl. Acad. Sci. USA 76 2979–2983CrossRefGoogle Scholar
  62. Storrie B and Madden EA 1990 Isolation of subcellular organelles. Methods Enzymol. 182 203–225Google Scholar
  63. Suleyman D, Akdag MZ, Kizil G, Kizil M, Cakir DU and Yokus B 2012 Effect of 900 MHz radiofrequency radiation on beta amyloid protein, protein carbonyl ad malondialdehyde in the brain. Electromag. Biol. Med. 31 67–74CrossRefGoogle Scholar
  64. Sundermann F, Marzouk A, Hopfer S, Zaharia O and Reid M 1985 Increased lipid peroxidation in tissues of nickel chloride-treated rats. Ann. Clin. Lab. Sci. 15 229–236Google Scholar
  65. Tanaka D, Nakada K, Takao K, Ogasawara E, Kasahara A, Sato A, Yonekawa H, Miyakawa T and Hayashi J 2008 Normal mitochondrial respiratory function is essential for spatial remote memory in mice. Mol. Brain. 16 1–21Google Scholar
  66. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC and Masters CL 2013 Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer disease: a prospective cohort study. Lancet Neurol. 12 357–367CrossRefPubMedGoogle Scholar
  67. Vorhees CV and Williams MT 2006 Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 1 848–858CrossRefPubMedPubMedCentralGoogle Scholar
  68. Wang B and Lai H 2000 Acute exposure to pulsed 2450-MHz microwaves affects water-maze performance of rats. Bioelectromagnetics 21 52–56CrossRefPubMedGoogle Scholar
  69. Webster KA 2012 Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future Cardiol. 8 863–884CrossRefPubMedPubMedCentralGoogle Scholar
  70. Xu S, Zhou Z, Zhang L, Yu Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, He M, Zhang G and Zhong M 2010 Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons. Brain Res. 22 189–196Google Scholar
  71. Yang Y, Zhang M, Kang X, Jiang C, Zhang H, Wang P and Li J 2015 Impaired adult hippocampal neurogenesis and cognitive ability in a mouse model of intrastriatal hemorrhage. Neurosci. Lett. 599 133–139CrossRefPubMedGoogle Scholar
  72. Zhang JQ, Gao BW, Wang J, Ren QL, Chen JF, Ma Q, Zhang ZJ. and Xing BS 2016 Critical role of FoxO1 in granulosa cell apoptosis caused by oxidative stress and protective effects of grape seed procyanidin B2. Oxid. Med. Cell Longev. 6147345 16Google Scholar
  73. Zhao L, Peng RY, Wang SM, Wang LF, Gao YB, Dong J, Li X and Su ZT 2012 Relationship between cognition function and hippocampus structure after long-term microwave exposure. Biomed. Environ. Sci. 2 182–188Google Scholar
  74. Zhao TY, Zou SP and Knapp PE 2007 Exposure of cell phone radiation upregulates apoptosis genes in primary cultures of neurons and astrocytes. Neurosci. Lett. 412 34–38CrossRefPubMedGoogle Scholar
  75. Zhi WJ, Peng RY, Li HJ, et al. 2017 Microwave radiation leading to shrinkage of dendritic spines in hippocampal neurons mediated by SNK-SPAR pathway. Brain Res. 1679 134–143CrossRefPubMedGoogle Scholar
  76. Zoukhri D and Kublin CL 2001 Impaired neurotransmitter release from lacrimal and salivary gland nerves of a murine model of Sjögren’s syndrome. Invest. Ophthalmol. Vis. Sci. 42 925–932PubMedPubMedCentralGoogle Scholar
  77. Zuo L, Hemmelgarn BT, Chuang CC and Best TM 2015 The role of oxidative stress-induced epigenetic alterations in amyloid- production in Alzheimer’s disease. Oxid. Med. Cell. Longev. Google Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of TechnologyBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of Electronics Engineering, Indian Institute of TechnologyBanaras Hindu UniversityVaranasiIndia

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