Advertisement

Environmental Science and Pollution Research

, Volume 23, Issue 24, pp 25343–25355 | Cite as

Glial markers and emotional memory in rats following acute cerebral radiofrequency exposures

  • Amélie Barthélémy
  • Amandine Mouchard
  • Marc Bouji
  • Kelly Blazy
  • Renaud Puigsegur
  • Anne-Sophie VillégierEmail author
Research Article

Abstract

The widespread mobile phone use raises concerns on the possible cerebral effects of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was reported in neuroanatomical structures of adaptive behaviors after a single RF EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to assess if neuronal injury and functional impairments were related to high SAR-induced astrogliosis. In addition, the level of beta amyloid 1–40 (Aβ 1–40) peptide was explored as a possible toxicity marker. Sprague Dawley male rats were exposed for 15 min at 0, 1.5, or 6 W/kg or for 45 min at 6 W/kg. Memory, emotionality, and locomotion were tested in the fear conditioning, the elevated plus maze, and the open field. Glial fibrillary acidic protein (GFAP, total and cytosolic fractions), myelin basic protein (MBP), and Aβ1–40 were quantified in six brain areas using enzyme-linked immunosorbent assay. According to our data, total GFAP was increased in the striatum (+114 %) at 1.5 W/kg. Long-term memory was reduced, and cytosolic GFAP was increased in the hippocampus (+119 %) and in the olfactory bulb (+46 %) at 6 W/kg (15 min). No MBP or Aβ1–40 expression modification was shown. Our data corroborates previous studies indicating RF EMF-induced astrogliosis. This study suggests that RF EMF-induced astrogliosis had functional consequences on memory but did not demonstrate that it was secondary to neuronal damage.

Keywords

Electromagnetic fields Astrogliosis Glial fibrillary acidic protein Myelin basic protein Beta amyloid 1–40 Fear conditioning Elevated plus maze Open field 

Notes

Acknowledgments

This work was funded by the Pr 190 of French Ministry of Ecology.

References

  1. Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I (2009) Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci 12:1567–1576CrossRefGoogle Scholar
  2. Ammari M, Brillaud E, Gamez C, Lecomte A, Sakly M, Abdelmelek H, de Seze R (2008a) Effect of a chronic GSM 900 MHz exposure on glia in the rat brain. Biomed Pharmacother 62:273–281CrossRefGoogle Scholar
  3. Ammari M, Jacquet A, Lecomte A, Sakly M, Abdelmelek H, de Seze R (2008b) Effect of head-only sub-chronic and chronic exposure to 900-MHz GSM electromagnetic fields on spatial memory in rats. Brain Inj 22:1021–1029CrossRefGoogle Scholar
  4. Arendash GW, Sanchez-Ramos J, Mori T, Mamcarz M, Lin X, Runfeldt M, Wang L, Zhang G, Sava V, Tan J, Cao C (2010) Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer’s disease mice. J Alzheimers Dis 19:191–210Google Scholar
  5. Ashok A, Rai NK, Tripathi S, Bandyopadhyay S (2015) Exposure to As-, Cd-, and Pb-mixture induces Abeta, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats. Toxicol Sci 143:64–80CrossRefGoogle Scholar
  6. Bas O, Odaci E, Mollaoglu H, Ucok K, Kaplan S (2009) Chronic prenatal exposure to the 900 megahertz electromagnetic field induces pyramidal cell loss in the hippocampus of newborn rats. Toxicol Ind Health 25:377–384CrossRefGoogle Scholar
  7. Bhasker AS, Sant B, Yadav P, Agrawal M, Lakshmana Rao PV (2014) Plant toxin abrin induced oxidative stress mediated neurodegenerative changes in mice. Neurotoxicology 44:194–203CrossRefGoogle Scholar
  8. Blanchard DC, Blanchard RJ (1972) Innate and conditioned reactions to threat in rats with amygdaloid lesions. J Comp Physiol Psychol 81:281–290Google Scholar
  9. Blasko I, Jungwirth S, Jellinger K, Kemmler G, Krampla W, Weissgram S, Wichart I, Tragl KH, Hinterhuber H, Fischer P (2008) Effects of medications on plasma amyloid beta (Abeta) 42: longitudinal data from the VITA cohort. J Psychiatr Res 42:946–955CrossRefGoogle Scholar
  10. Boran MS, Garcia A (2007) The cyclic GMP-protein kinase G pathway regulates cytoskeleton dynamics and motility in astrocytes. J Neurochem 102:216–230CrossRefGoogle Scholar
  11. Bouji M, Lecomte A, Hode Y, de Seze R, Villegier AS (2012) Effects of 900 MHz radiofrequency on corticosterone, emotional memory and neuroinflammation in middle-aged rats. Exp Gerontol 47:444–451CrossRefGoogle Scholar
  12. Bouji M, Lecomte A, Gamez C, Blazy K, Villegier AS (2016) Neurobiological effects of repeated radiofrequency exposures in male senescent rats. BiogerontologyGoogle Scholar
  13. Brillaud E, Morillion D, de Seze R (2005) Modest environmental enrichment: effect on a radial maze validation and well being of rats. Brain Res 1054:174–182CrossRefGoogle Scholar
  14. Brillaud E, Piotrowski A, de Seze R (2007) Effect of an acute 900 MHz GSM exposure on glia in the rat brain: a time-dependent study. Toxicology 238:23–33CrossRefGoogle Scholar
  15. Cassel JC, Cosquer B, Galani R, Kuster N (2004) Whole-body exposure to 2.45 GHz electromagnetic fields does not alter radial-maze performance in rats. Behav Brain Res 155:37–43CrossRefGoogle Scholar
  16. Coria F, Berciano MT, Berciano J, Lafarga M (1984) Axon membrane remodeling in the lead-induced demyelinating neuropathy of the rat. Brain Res 291:369–372CrossRefGoogle Scholar
  17. Cosquer B, Vasconcelos AP, Frohlich J, Cassel JC (2005) Blood-brain barrier and electromagnetic fields: effects of scopolamine methylbromide on working memory after whole-bodyGoogle Scholar
  18. Court-Kowalski S, Finnie JW, Manavis J, Blumbergs PC, Helps SC, Vink R (2015) Effect of long-term (2 years) exposure of mouse brains to global system for mobile communication (GSM) radiofrequency fields on astrocytic immunoreactivity. Bioelectromagnetics 36:245–250CrossRefGoogle Scholar
  19. Daniels WM, Pietersen CY, Carstens ME, Stein DJ (2004) Maternal separation in rats leads to anxiety-like behavior and a blunted ACTH response and altered neurotransmitter levels in response to a subsequent stressor. Metab Brain Dis 19:3–14CrossRefGoogle Scholar
  20. Deng Z, Fu H, Xiao Y, Zhang B, Sun G, Wei Q, Ai B, Hu Q (2015) Effects of selenium on lead-induced alterations in Abeta production and Bcl-2 family proteins. Environ Toxicol Pharmacol 39:221–228CrossRefGoogle Scholar
  21. Dragicevic N, Bradshaw PC, Mamcarz M, Lin X, Wang L, Cao C, Arendash GW (2011) Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer’s transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit? Neuroscience 185:135–149CrossRefGoogle Scholar
  22. Dubreuil D, Jay T, Edeline JM (2002) Does head-only exposure to GSM-900 electromagnetic fields affect the performance of rats in spatial learning tasks? Behav Brain Res 129:203–210CrossRefGoogle Scholar
  23. Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes—implications for their role in neurologic disease. Neuroscience 54:15–36CrossRefGoogle Scholar
  24. Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214CrossRefGoogle Scholar
  25. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000. Neurochem Res 25:1439–1451CrossRefGoogle Scholar
  26. Eulitz C, Ullsperger P, Freude G, Elbert T (1998) Mobile phones modulate response patterns of human brain activity. Neuroreport 9:3229–3232CrossRefGoogle Scholar
  27. Fragopoulou AF, Samara A, Antonelou MH, Xanthopoulou A, Papadopoulou A, Vougas K, Koutsogiannopoulou E, Anastasiadou E, Stravopodis DJ, Tsangaris GT, Margaritis LH (2012) Brain proteome response following whole body exposure of mice to mobile phone or wireless DECT base radiation. Electromagn Biol Med 31:250–274CrossRefGoogle Scholar
  28. Fritze K, Wiessner C, Kuster N, Sommer C, Gass P, Hermann DM, Kiessling M, Hossmann KA (1997) Effect of global system for mobile communication microwave exposure on the genomic response of the rat brain. Neuroscience 81:627–639CrossRefGoogle Scholar
  29. Grafstrom G, Nittby H, Brun A, Malmgren L, Persson BR, Salford LG, Eberhardt J (2008) Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation. Brain Res Bull 77:257–263CrossRefGoogle Scholar
  30. Haarala C, Aalto S, Hautzel H, Julkunen L, Rinne JO, Laine M, Krause B, Hamalainen H (2003) Effects of a 902 MHz mobile phone on cerebral blood flow in humans: a PET study. Neuroreport 14:2019–2023CrossRefGoogle Scholar
  31. Haarala C, Takio F, Rintee T, Laine M, Koivisto M, Revonsuo A, Hamalainen H (2007) Pulsed and continuous wave mobile phone exposure over left versus right hemisphere: effects on human cognitive function. Bioelectromagnetics 28:289–295CrossRefGoogle Scholar
  32. Hardell L, Carlberg M (2013) Use of mobile and cordless phones and survival of patients with glioma. Neuroepidemiology 40:101–108CrossRefGoogle Scholar
  33. Hernandez-Zimbron LF, Rivas-Arancibia S (2015) Oxidative stress caused by ozone exposure induces beta-amyloid 1-42 overproduction and mitochondrial accumulation by activating the amyloidogenic pathway. Neuroscience 304:340–348CrossRefGoogle Scholar
  34. Hewett JA (2009) Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system. J Neurochem 110:1717–1736CrossRefGoogle Scholar
  35. Ikegami M, Uemura T, Kishioka A, Sakimura K, Mishina M (2014) Striatal dopamine D1 receptor is essential for contextual fear conditioning. Sci Rep 4:3976Google Scholar
  36. INTERPHONE group (2010) Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case-control study. Int J Epidemiol 39:675–694CrossRefGoogle Scholar
  37. Keetley V, Wood AW, Spong J, Stough C (2006) Neuropsychological sequelae of digital mobile phone exposure in humans. Neuropsychologia 44:1843–1848CrossRefGoogle Scholar
  38. Kim TH, Huang TQ, Jang JJ, Kim MH, Kim HJ, Lee JS, Pack JK, Seo JS, Park WY (2008) Local exposure of 849 MHz and 1763 MHz radiofrequency radiation to mouse heads does not induce cell death or cell proliferation in brain. Exp Mol Med 40:294–303CrossRefGoogle Scholar
  39. Koivisto M, Krause CM, Revonsuo A, Laine M, Hamalainen H (2000) The effects of electromagnetic field emitted by GSM phones on working memory. Neuroreport 11:1641–1643CrossRefGoogle Scholar
  40. Krause CM, Sillanmaki L, Koivisto M, Haggqvist A, Saarela C, Revonsuo A, Laine M, Hamalainen H (2000) Effects of electromagnetic field emitted by cellular phones on the EEG during a memory task. Neuroreport 11:761–764CrossRefGoogle Scholar
  41. Krause CM, Haarala C, Sillanmaki L, Koivisto M, Alanko K, Revonsuo A, Laine M, Hamalainen H (2004) Effects of electromagnetic field emitted by cellular phones on the EEG during an auditory memory task: a double blind replication study. Bioelectromagnetics 25:33–40CrossRefGoogle Scholar
  42. Lai H (2004) Interaction of microwaves and a temporally incoherent magnetic field on spatial learning in the rat. Physiol Behav 82:785–789CrossRefGoogle Scholar
  43. Lai H, Carino MA, Horita A, Guy AW (1990) Corticotropin-releasing factor antagonist blocks microwave-induced decreases in high-affinity choline uptake in the rat brain. Brain Res Bull 25:609–612CrossRefGoogle Scholar
  44. Lee TM, Lam PK, Yee LT, Chan CC (2003) The effect of the duration of exposure to the electromagnetic field emitted by mobile phones on human attention. Neuroreport 14:1361–1364CrossRefGoogle Scholar
  45. Lee YK, Yuk DY, Lee JW, Lee SY, Ha TY, KW O, Yun YP, Hong JT (2009) (−)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency. Brain Res 1250:164–174CrossRefGoogle Scholar
  46. Leveque P, Dale C, Veyret B, Wiart J (2004) Dosimetric analysis of a 900-MHz rat head exposure system. IEEE Trans Microwave Theory Tech:2076–2083Google Scholar
  47. Lu Y, He M, Zhang Y, Xu S, Zhang L, He Y, Chen C, Liu C, Pi H, Yu Z, Zhou Z (2014) Differential pro-inflammatory responses of astrocytes and microglia involve STAT3 activation in response to 1800 MHz radiofrequency fields. PLoS One 9:e108318CrossRefGoogle Scholar
  48. Ma F, Liu D (2015) 17beta-trenbolone, an anabolic-androgenic steroid as well as an environmental hormone, contributes to neurodegeneration. Toxicol Appl Pharmacol 282:68–76CrossRefGoogle Scholar
  49. Ma T, Wu X, Cai Q, Wang Y, Xiao L, Tian Y, Li H (2015) Lead poisoning disturbs oligodendrocytes differentiation involved in decreased expression of NCX3 inducing intracellular calcium overload. Int J Mol Sci 16:19096–19110CrossRefGoogle Scholar
  50. Maier R, Greter SE, Maier N (2004) Effects of pulsed electromagnetic fields on cognitive processes—a pilot study on pulsed field interference with cognitive regeneration. Acta Neurol Scand 110:46–52CrossRefGoogle Scholar
  51. Maskey D, Pradhan J, Aryal B, Lee CM, Choi IY, Park KS, Kim SB, Kim HG, Kim MJ (2010) Chronic 835-MHz radiofrequency exposure to mice hippocampus alters the distribution of calbindin and GFAP immunoreactivity. Brain Res 1346:237–246CrossRefGoogle Scholar
  52. Maskey D, Kim HJ, Kim HG, Kim MJ (2012) Calcium-binding proteins and GFAP immunoreactivity alterations in murine hippocampus after 1 month of exposure to 835 MHz radiofrequency at SAR values of 1.6 and 4.0 W/kg. Neurosci Lett 506:292–296CrossRefGoogle Scholar
  53. Mausset AL, de Seze R, Montpeyroux F, Privat A (2001) Effects of radiofrequency exposure on the GABAergic system in the rat cerebellum: clues from semi-quantitative immunohistochemistry. Brain Res 912:33–46CrossRefGoogle Scholar
  54. Mausset-Bonnefont AL, Hirbec H, Bonnefont X, Privat A, Vignon J, de Seze R (2004) Acute exposure to GSM 900-MHz electromagnetic fields induces glial reactivity and biochemical modifications in the rat brain. Neurobiol Dis 17:445–454CrossRefGoogle Scholar
  55. Middeldorp J, Hol EM (2011) GFAP in health and disease. Prog Neurobiol 93:421–443CrossRefGoogle Scholar
  56. Morin-Richaud C, Feldblum S, Privat A (1998) Astrocytes and oligodendrocytes reactions after a total section of the rat spinal cord. Brain Res 783:85–101CrossRefGoogle Scholar
  57. Morley JE, Farr SA, Banks WA, Johnson SN, Yamada KA, Xu L (2010) A physiological role for amyloid-beta protein:enhancement of learning and memory. J Alzheimers Dis 19:441–449Google Scholar
  58. Nishiyama A, Komitova M, Suzuki R, Zhu X (2009) Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci 10:9–22CrossRefGoogle Scholar
  59. Nittby H, Grafstrom G, Tian DP, Malmgren L, Brun A, Persson BR, Salford LG, Eberhardt J (2008) Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation. Bioelectromagnetics 29:219–232CrossRefGoogle Scholar
  60. O’Callaghan JP (1991) Quantification of glial fibrillary acidic protein: comparison of slot-immunobinding assays with a novel sandwich ELISA. Neurotoxicol Teratol 13:275–281CrossRefGoogle Scholar
  61. Petitdant N, Lecomte A, Robidel F, Gamez C, Blazy K, Villégier A (2016) Cerebral radiofrequency exposures during adolescence: impact on astrocytes and brain functions in healthy and pathologic rat models. BioelectromagneticsGoogle Scholar
  62. Preece AW, Iwi G, Davies-Smith A, Wesnes K, Butler S, Lim E, Varey A (1999) Effect of a 915-MHz simulated mobile phone signal on cognitive function in man. Int J Radiat Biol 75:447–456CrossRefGoogle Scholar
  63. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3–33CrossRefGoogle Scholar
  64. Quinn JJ, Ma QD, Tinsley MR, Koch C, Fanselow MS (2008) Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories. Learn Mem 15:368–372CrossRefGoogle Scholar
  65. Rapanelli M, Frick LR, Zanutto BS (2011) Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus. PLoS One 6:e14713CrossRefGoogle Scholar
  66. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686CrossRefGoogle Scholar
  67. Schang AL, Van Steenwinckel J, Chevenne D, Alkmark M, Hagberg H, Gressens P, Fleiss B (2014) Failure of thyroid hormone treatment to prevent inflammation-induced white matter injury in the immature brain. Brain Behav Immun 37:95–102Google Scholar
  68. Schiffer D, Giordana MT, Migheli A, Giaccone G, Pezzotta S, Mauro A (1986) Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain. Brain Res 374:110–118CrossRefGoogle Scholar
  69. Schmidt-Kastner R, Szymas J (1990) Immunohistochemistry of glial fibrillary acidic protein, vimentin and S-100 protein for study of astrocytes in hippocampus of rat. J Chem Neuroanat 3:179–192Google Scholar
  70. Sienkiewicz ZJ, Blackwell RP, Haylock RG, Saunders RD, Cobb BL (2000) Low-level exposure to pulsed 900 MHz microwave radiation does not cause deficits in the performance of a spatial learning task in mice. Bioelectromagnetics 21:151–158CrossRefGoogle Scholar
  71. Silverberg GD, Miller MC, Messier AA, Majmudar S, Machan JT, Donahue JE, Stopa EG, Johanson CE (2010) Amyloid deposition and influx transporter expression at the blood-brain barrier increase in normal aging. J Neuropathol Exp Neurol 69:98–108CrossRefGoogle Scholar
  72. Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647CrossRefGoogle Scholar
  73. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35CrossRefGoogle Scholar
  74. Spitzer P, Herrmann M, Klafki HW, Smirnov A, Lewczuk P, Kornhuber J, Wiltfang J, Maler JM (2010) Phagocytosis and LPS alter the maturation state of beta-amyloid precursor protein and induce different Abeta peptide release signatures in human mononuclear phagocytes. J Neuroinflammation 7:59CrossRefGoogle Scholar
  75. Thorlin T, Rouquette JM, Hamnerius Y, Hansson E, Persson M, Bjorklund U, Rosengren L, Ronnback L, Persson M (2006) Exposure of cultured astroglial and microglial brain cells to 900 MHz microwave radiation. Radiat Res 166:409–421CrossRefGoogle Scholar
  76. Tseng WC, Lu KS, Lee WC, Chien CL (2006) Redistribution of GFAP and alphaB-crystallin after thermal stress in C6 glioma cell line. J Biomed Sci 13:681–694CrossRefGoogle Scholar
  77. Watilliaux A, Edeline JM, Leveque P, Jay TM, Mallat M (2011) Effect of exposure to 1,800 MHz electromagnetic fields on heat shock proteins and glial cells in the brain of developing rats. Neurotox Res 20(2):109–119CrossRefGoogle Scholar
  78. Wenzel J, Lammert G, Meyer U, Krug M (1991) The influence of long-term potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain. Brain Res 560:122–131CrossRefGoogle Scholar
  79. Zhao JW, Raha-Chowdhury R, Fawcett JW, Watts C (2009) Astrocytes and oligodendrocytes can be generated from NG2+ progenitors after acute brain injury: intracellular localization of oligodendrocyte transcription factor 2 is associated with their fate choice. Eur J Neurosci 29:1853–1869CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institut national de l’environnement industriel et des risques (INERIS), Unité de Toxicologie ExpérimentaleParc Technologique ALATAVerneuil-en-HalatteFrance
  2. 2.Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212StrasbourgFrance
  3. 3.Institut des Maladies Neurodégénératives CNRS UMR5293 Université de BordeauxBordeauxFrance
  4. 4.Campus des sciences et technologiesUniversité Saint-JosephDekwanehLebanon
  5. 5.Unité mixte PERITOX EA 4285-UM INERIS 01 Laboratoire Périnatalité et risques toxicologiques CHU Amiens-Picardie HôpitalSalouëlFrance
  6. 6.Sous-direction de la police technique et scientifiqueEcullyFrance

Personalised recommendations