Skip to main content

Advertisement

SpringerLink
Log in

Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Mobile phone providers use electromagnetic radiation (EMR) with frequencies ranging from 900 to 1800 MHz. The increasing use of mobile phones has been accompanied by several potentially pathological consequences, such as neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN, high temperature and oxidative stress. We investigated the contribution TRPV1 to mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800 MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of the week during the one year. The 900 and 1800 MHz EMR exposure induced increases in TRPV1 currents, intracellular free calcium influx (Ca2+), reactive oxygen species (ROS) production, mitochondrial membrane depolarization (JC-1), apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These deleterious processes were further increased in the 1800 MHz experimental group compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative stress, programmed cell death and Ca2+ entry pathway through TRPV1 activation in the HIPPON and DRGN of rats were increased in the rat model following exposure to 900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and 1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Effect of 900 and 1800 MHz EMR exposure on [Ca2+]i concentration through TRPV1 gate in HIPPON (a) and DRGN (b) of rats.
Fig. 2: Effect of 900 and 1800 MHz EMR exposure on TRPV1 channel activation in DRGN of rat
Fig. 3: Effect of 900 and 1800 MHz EMR on the apoptosis level, caspase 3 and 9 activities through TRPV1 channel activations in the HIPPON (a, c and e) and DRGN (b, d and f) of rats
Fig. 4: Effect of 900 and 1800 MHz EMR on the intracellular ROS production and mitochondrial membrane depolarization (JC-1) levels through TRPV1 channel activations in the HIPPO (a and c) and DRGN (b and d) of rats

Similar content being viewed by others

Abbreviations

[Ca2+]i :

Intracellular free calcium ion

CapN:

Capsaicin

CapZ:

Capsazepine

DHR:

Dihydrorhodamine

DRGN:

Dorsal root ganglion neuron

EMR:

Electromagnetic radiation

HIPPON:

Hippocampal neuron

PUFA:

Polyunsaturated fatty acid

ROS:

Reactive oxygen species

SAR:

Specific absorption rate

TRP:

Transient receptor potential

TRPV1:

Transient receptor potential vanilloid 1

VGGC:

Voltage gated calcium channel

W.C.:

Whole cell

References

  • Bas O, Odaci E, Kaplan S, Acer N, Ucok K, Colakoglu S (2009) 900 MHz electromagnetic field exposure affects qualitative and quantitative features of hippocampal pyramidal cells in the adult female rat. Brain Res 1265:178–185

    Article  PubMed  CAS  Google Scholar 

  • Bejarano I, Redondo PC, Espino J, Rosado JA, Paredes SD, Barriga C, Reiter RJ, Pariente JA, Rodríguez AB (2009) Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells. J Pineal Res 46:392–400

    Article  PubMed  CAS  Google Scholar 

  • Bodera P, Stankiewicz W, Zawada K, Antkowiak B, Paluch M, Kieliszek J, Kalicki B, Bartosiński A, Wawer I (2013) Changes in antioxidant capacity of blood due to mutual action of electromagnetic field (1800 MHz) and opioid drug (tramadol) in animal model of persistent inflammatory state. Pharmacol Rep 65(2):421–428

    Article  PubMed  CAS  Google Scholar 

  • Bortkiewicz A, Gadzicka E, Szymczak W, Zmyślony M (2012) Changes in tympanic temperature during the exposure to electromagnetic fields emitted by mobile phone. Int J Occup Med Environ Health 25(2):145–150

    Article  PubMed  Google Scholar 

  • Carballo-Quintás M, Martínez-Silva I, Cadarso-Suárez C, Alvarez-Figueiras M, Ares-Pena FJ, López-Martín E (2011) A study of neurotoxic biomarkers, c-fos and GFAP after acute exposure to GSM radiation at 900 MHz in the picrotoxin model of rat brains. Neurotoxicology 32(4):478–494

    Article  PubMed  CAS  Google Scholar 

  • Carrasco C, Rodríguez BA, Pariente JA (2015) Melatonin as a stabilizer of mitochondrial function: Role in diseases and aging. Turk J Biol 39:822–831

    Article  CAS  Google Scholar 

  • Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398(6726):436–441

    Article  PubMed  CAS  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  PubMed  CAS  Google Scholar 

  • Çetin H, Nazıroğlu M, Çelik Ö, Yüksel M, Pastacı N, Özkaya MO (2014) Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring. J Matern Fetal Neonatal Med 27(18):1915–1921

    Article  PubMed  Google Scholar 

  • Çiğ B, Nazıroğlu M (2015) Investigation of the effects of distance from sources on apoptosis, oxidative stress and cytosolic calcium accumulation via TRPV1 channels induced by mobile phones and Wi-Fi in breast cancer cells. Biochim Biophys Acta 1848(10 Pt B):2756–2765

    Article  PubMed  Google Scholar 

  • Cinar N, Sahin S, Erdinc OO (2013) What is the impact of electromagnetic waves on epileptic seizures? Med Sci Monit Basic Res 19:141–145

    Article  PubMed  PubMed Central  Google Scholar 

  • Cossarizza A, Baccarani-Contri M, Kalashnikova G, Franceschi C (1993) A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem Biophys Res Commun 197:40–45

    Article  PubMed  CAS  Google Scholar 

  • Crawford DC, Moulder KL, Gereau RW IV, Story GM, Mennerick S (2009) Comparative effects of heterologous TRPV1 and TRPM8 expression in rat hippocampal neurons. PLoS One 4(12):e8166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Tommaso M, Rossi P, Falsaperla R, Francesco Vde V, Santoro R, Federici A (2009) Mobile phones exposure induces changes of contingent negative variation in humans. Neurosci Lett 464(2):79–83

    Article  PubMed  CAS  Google Scholar 

  • Ghazizadeh V, Nazıroğlu M (2014) Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats. Metab Brain Dis 29(3):787–799

    Article  PubMed  CAS  Google Scholar 

  • Gökçek-Saraç Ç, Er H, Kencebay Manas C, Kantar Gok D, Özen Ş, Derin N (2017) Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway. Int J Radiat Biol 93(9):980–989

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658

    Article  PubMed  CAS  Google Scholar 

  • Han Q, Kim YH, Wang X, Liu D, Zhang ZJ, Bey AL, Lay M, Chang W, Berta T, Zhang Y, Jiang YH, Ji RR (2016) SHANK3 Deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons. Neuron 92(6):1279–1293

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hou Q, Wang M, Wu S, Ma X, An G, Liu H, Xie F (2015) Oxidative changes and apoptosis induced by 1800-MHz electromagnetic radiation in NIH/3T3 cells. Electromagn Biol Med 34:85–92

    Article  PubMed  CAS  Google Scholar 

  • Ibi M, Matsuno K, Shiba D, Katsuyama M, Iwata K, Kakehi T, Nakagawa T, Sango K, Shirai Y, Yokoyama T, Kaneko S, Saito N, Yabe-Nishimura C (2008) Reactive oxygen species derived from NOX1/NADPH oxidase enhance inflammatory pain. J Neurosci 28:9486–9494

    Article  PubMed  CAS  Google Scholar 

  • Jin Z, Zong C, Jiang B, Zhou Z, Tong J, Cao Y (2012) The effect of combined exposure of 900 MHz radiofrequency fields and doxorubicin in HL-60 cells. PLoS One 7(9):e46102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Joubert V, Bourthoumieu S, Leveque P, Yardin C (2008) Apoptosis is induced by radiofrequency fields through the caspase-independent mitochondrial pathway in cortical neurons. Radiat Res 169:38–45

    Article  PubMed  CAS  Google Scholar 

  • Kahya MC, Nazıroğlu M, Çiğ B (2014) Selenium reduces mobile phone (900 MHz)-induced oxidative stress, mitochondrial function, and apoptosis in breast cancer cells. Biol Trace Elem Res 160(2):285–293

    Article  PubMed  CAS  Google Scholar 

  • Kesari KK, Siddiqui MH, Meena R, Verma HN, Kumar S (2013) Cell phone radiation exposure on brain and associated biological systems. Indian J Exp Biol 51:187–200

    PubMed  CAS  Google Scholar 

  • Kim JH, DH Y, Kim HR (2017) Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure. Korean J Physiol Pharmacol 21(2):179–188

    Article  PubMed  PubMed Central  Google Scholar 

  • Köktürk S, Yardimoglu M, Celikozlu SD, Dolanbay EG, Cimbiz A (2013) Effect of Lycopersicon esculentum extract on apoptosis in the rat cerebellum, following prenatal and postnatal exposure to an electromagnetic field. Exp Ther Med 6(1):52–56

    Article  PubMed  PubMed Central  Google Scholar 

  • Köylü H, Mollaoglu H, Ozguner F, Naziroglu M, Delibas N (2006) Melatonin modulates 900 Mhz microwave-induced lipid peroxidation changes in rat brain. Toxicol Ind Health 22(5):211–216

    Article  PubMed  Google Scholar 

  • Kumar VS, Gopalakrishnan A, Nazıroğlu M, Rajanikant GK (2014) Calcium ion--the key player in cerebral ischemia. Curr Med Chem 21:2065–2075

    Article  PubMed  CAS  Google Scholar 

  • Nazıroğlu M, Çelik Ö, Özgül C, Çiğ B, Doğan S, Bal R, Gümral N, Rodríguez AB, Pariente JA (2012b) 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 105:683–692

    Article  PubMed  CAS  Google Scholar 

  • Nazıroğlu M, Çiğ B, Blum W, Vizler C, Buhala A, Marton A, Katona R, Jósvay K, Schwaller B, Oláh Z, Pecze L (2017) Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. PLoS One 12(6):e0179950

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nazıroğlu M, Özkan FF, Hapil SR, Ghazizadeh V, Çiğ B (2015) Epilepsy but not mobile phone frequency (900 MHz) induces apoptosis and calcium entry in hippocampus of epileptic rat: involvement of TRPV1 channels. J Membr Biol 248(1):83–91

    Article  PubMed  CAS  Google Scholar 

  • Nazıroğlu M, Tokat S, Demirci S (2012a) Role of melatonin on electromagnetic radiation-induced oxidative stress and Ca2+ signaling molecular pathways in breast cancer. J Recept Signal Transduct Res 32(6):290–297

    Article  PubMed  CAS  Google Scholar 

  • Nazıroğlu M, Yüksel M, Köse SA, Özkaya MO (2013) Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress and reproductive signaling pathways in females and males. J Membr Biol 246(12):869–875

    Article  PubMed  CAS  Google Scholar 

  • Nazıroğlu M (2017) Activation of TRPM2 and TRPV1 channels in dorsal root ganglion by NADPH oxidase and protein kinase C molecular pathways: a patch clamp study. J Mol Neurosci 61:425–435

    Article  PubMed  CAS  Google Scholar 

  • O'Connor RP, Madison SD, Leveque P, Roderick HL, Bootman MD (2010) Exposure to GSM RF fields does not affect calcium homeostasis in human endothelial cells, rat pheocromocytoma cells or rat hippocampal neurons. PLoS One 5(7):e11828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ogawa N, Kurokawa T, Fujiwara K, Polat OK, Badr H, Takahashi N, Mori Y (2016) Functional and structural divergence in human TRPV1 channel subunits by oxidative cysteine modification. J Biol Chem 291:4197–4210

    Article  PubMed  CAS  Google Scholar 

  • Özorak A, Nazıroğlu M, Çelik Ö, Yüksel M, Özçelik D, Özkaya MO, Çetin H, Kahya MC, Kose SA (2013) Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative stress and elements in kidney and testis of rats during pregnancy and the development of offspring. Biol Trace Elem Res 156:221–229

    Article  PubMed  CAS  Google Scholar 

  • Pall ML (2013) Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med 17(8):958–965

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pecze L, Blum W, Schwaller B (2013) Mechanism of capsaicin receptor TRPV1-mediated toxicity in pain-sensing neurons focusing on the effects of Na(+)/Ca(2+) fluxes and the Ca(2+)-binding protein calretinin. Biochim Biophys Acta 1833:1680–1691

    Article  PubMed  CAS  Google Scholar 

  • Platano D, Mesirca P, Paffi A, Pellegrino M, Liberti M, Apollonio F, Bersani F, Aicardi G (2007) Acute exposure to low-level CW and GSM-modulated 900 MHz radiofrequency does not affect Ba 2+ currents through voltage-gated calcium channels in rat cortical neurons. Bioelectromagnetics 28(8):599–607

    Article  PubMed  CAS  Google Scholar 

  • Rohm B, Riedel A, Ley JP, Widder S, Krammer GE, Somoza V (2015) Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase acetyl-coenzyme A synthetase activity in Caco-2 cells. Food Funct 6(1):173–185

    Article  PubMed  CAS  Google Scholar 

  • Shahin S, Banerjee S, Singh SP, Chaturvedi CM (2015) 2.45 GHz microwave radiation impairs learning and spatial Memory via oxidative/nitrosative stress induced p53-dependent/independent hippocampal apoptosis: Molecular basis and underlying mechanism. Toxicol Sci 148:380–399

    Article  PubMed  CAS  Google Scholar 

  • Shi Y (2002) Apoptosome: the cellular engine for the activation of caspase-9. Structure 10(3):285–288

    Article  PubMed  CAS  Google Scholar 

  • Sun ZC, Ge JL, Guo B, Guo J, Hao M, YC W, Lin YA, La T, Yao PT, Mei YA, Feng Y, Xue L (2016) Extremely low frequency electromagnetic fields facilitate vesicle endocytosis by increasing presynaptic calcium channel expression at a central synapse. Sci Rep 6:21774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Türedi S, Hancı H, Topal Z, Ünal D, Mercantepe T, Bozkurt İ, Kaya H, Odacı E (2015) The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart. Electromagn Biol Med. 34:390–397

    Article  PubMed  CAS  Google Scholar 

  • Xu S, Zhou Z, Zhang L, Yu Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, He M, Zhang G, Zhong M (2010) Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons. Brain Res 1311:189–196

    Article  PubMed  CAS  Google Scholar 

  • Yüksel M, Nazıroğlu M, Özkaya MO (2016) Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring. Endocrine 52:352–362

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The abstract of the study was published in the Thermal Biology 2017 International Symposium, September 4, 2017, Kyoto, Japan. The authors wish to thank the technician Fatih Şahin (BSN Sağlık Analiz, ARGE, Danışmanlık, Sağlık ve Tarım Ltd., Isparta, Turkey) and Dr. Nady Braidy (School of Psychiatry, Faculty of Medicine, University of New South Wales, Randwick Australia) for helping with the patch-clamp analyses and polishing English, respectively.

Author information

Author notes

  1. Mustafa Nazıroğlu

    Present address: Neuroscience Research Center, Suleyman Demirel University, TR-32260, Isparta, Turkey

Authors and Affiliations

  1. Departmant of Neurosurgery, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Kemal Ertilav

  2. Department of Plastic Reconstructive and Aesthetic Surgery, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    Fuat Uslusoy

  3. Departmant of Neurosurgery, Yunusemre General State Hospital, Eskişehir, Turkey

    Serdar Ataizi

Authors
  1. Kemal Ertilav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fuat Uslusoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Serdar Ataizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mustafa Nazıroğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MN formulated the present hypothesis and was responsible for writing the report. KE, FU and SA were responsible for analyses of spectrofluorometer and plate reader.

Corresponding author

Correspondence to Mustafa Nazıroğlu.

Ethics declarations

Disclosures

None of the authors have any to disclose. All authors approved the final manuscript.

Financial disclosure

There is no financial support for the current study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ertilav, K., Uslusoy, F., Ataizi, S. et al. Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats. Metab Brain Dis 33, 753–763 (2018). https://doi.org/10.1007/s11011-017-0180-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-017-0180-4

Keywords

Search

Navigation