Abstract
Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca2+ permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca2+ entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca2+ influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca2+, reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and −9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca2+ increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca2+ influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca2+ channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca2+ influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca2+ influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.
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Abbreviations
- [Ca2+]i :
-
Intracellular Ca2+
- DMSO:
-
Dimethyl sulfoxide
- DRG:
-
Dorsal root ganglion
- EMR:
-
Electromagnetic radiation
- ROS:
-
Reactive oxygen species
- TRP:
-
Transient receptor potential
- TRPV1:
-
Transient receptor potential vanilloid 1
- WC:
-
Whole cell
- CAP:
-
Capsaicin
- CPZ:
-
Capzapine
References
Adey WR, Bawin SM, Lawrence AF (1982) Effects of weak amplitude-modulated microwave fields on calcium efflux from awake cat cerebral cortex. Bioelectromagnetics 3:295–307
Aït-Aïssa S, Billaudel B, Poulletier de Gannes F, Ruffié G, Duleu S, Hurtier A, Haro E, Taxile M, Athané A, Geffard M, Wu T, Wiart J, Bodet D, Veyret B, Lagroye I (2012) In utero and early-life exposure of rats to a Wi-Fi signal: screening of immune markers in sera and gestational outcome. Bioelectromagnetics 33:410–420
Ammari M, Lecomte A, Sakly M, Abdelmelek H, de-Seze R (2008) Exposure to GSM 900 MHz electromagnetic fields affects cerebral cytochrome c oxidase activity. Toxicology 250(1):70–74
Bawin SM, Adey WR, Sabbot IM (1978) Ionic factors in release of 45Ca2+ from chicken cerebral tissue by electromagnetic fields. Proc Natl Acad Sci U S A 75(12):6314–6318
Berman E, Carter HB, House D (1981) Observations of rat fetuses after irradiation with 2450 MHz (CW) microwaves. J Microw Power 16:9–13
Berman E, Carter HB, House D (1982) Observations of Syrian hamster fetuses after exposure to 2450-MHz microwaves. J Microw Power 17:107–112
Bhaskaran MD, Smith BN (2010) Effects of TRPV1 activation on synaptic excitation in the dentate gyrus of a mouse model of temporal lobe epilepsy. Exp Neurol 223:529–536
Burkhardt M, Pokovic K, Gnos M, Schmid T, Kuster N (1996) Numerical and experimental dosimetry of petri dish exposure setups. Bioelectromagnetics 17:483–493
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 32:478–494
Celik O, Nazıroğlu M (2012) Melatonin modulates apoptosis and TRPM2 channels in transfected cells activated by oxidative stress. Physiol Behav 107:458–465
Dasdag S, Akdag MZ, Ulukaya E, Uzunlar AK, Ocak AR (2009) Effect of mobile phone exposure on apoptotic glial cells and status of oxidative stress in rat brain. Electromagn Biol Med 28:342–354
Dericioglu N, Soylemezoglu F, Gursoy-Ozdemir Y, Akalan N, Saygi S, Dalkara T (2013) Cell death and survival mechanisms are concomitantly active in the hippocampus of patients with mesial temporal sclerosis. Neuroscience 237C:56–65
Edwards JG, Gibson HE, Jensen T, Nugent F, Walther C, Blickenstaff J, Kauer JA (2012) A novel non-CB1/TRPV1 endocannabinoid-mediated mechanism depresses excitatory synapses on hippocampal CA1 interneurons. Hippocampus 22:209–221
Espino J, Mediero M, Bejarano I, Lozano GM, Ortiz A, García JF, Pariente JA, Rodríguez AB (2009) Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients. Reprod Biol Endor 7:11
Espino J, Bejarano I, Redondo PC, Rosado JA, Barriga C, Reiter RJ, Pariente JA, Rodríguez AB (2010) Melatonin reduces apoptosis induced by calcium signaling in human leukocytes: evidence for the involvement of mitochondria and bax activation. J Membr Biol 233:105–118
Espino J, Bejarano I, Paredes SD, Barriga C, Rodríguez AB, Pariente JA (2011) Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions. J Pineal Res 51:195–206
Fukui Y, Hoshino K, Inouye M, Kameyama Y (1992) Effects of hyperthermia induced by microwave irradiation on brain development in mice. J Radiat Res 33:1–10
González A, Pariente JA, Salido GM (2007) Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes. Brain Res 1178:28–37
Grassi C, D’Ascenzo M, Torsello A, Martinotti G, Wolf F, Cittadini A, Azzena GB (2004) Effects of 50 Hz electromagnetic fields on voltage-gated Ca2+ channels and their role in modulation of neuroendocrine cell proliferation and death. Cell Calcium 35:307–315
Grynkiewicz C, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450
Hong S, Agresta L, Guo C, Wiley JW (2008) The TRPV1 receptor is associated with preferential stress in large dorsal root ganglion neurons in early diabetic sensory neuropathy. J Neurochem 105:1212–1222
Ikeda N, Hayashida O, Kameda H, Ito H, Matsuda T (1994) Experimental study on thermal damage to dog normal brain. Int J Hyperth 10:553–561
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
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
Kiani-Esfahani A, Tavalaee M, Deemeh MR, Hamiditabar M, Nasr-Esfahani MH (2012) DHR123: an alternative probe for assessment of ROS in human spermatozoa. Syst Biol Reprod Med 58:168–174
Kim SR, Lee DY, Chung ES, Oh UT, Kim SU, Jin BK (2005) Transient receptor potential vanilloid subtype 1 mediates cell death of mesencephalic dopaminergic neurons in vivo and in vitro. J Neurosci 25:662–671
Kovács R, Kardos J, Heinemann U, Kann O (2005) Mitochondrial calcium ion and membrane potential transients follow the pattern of epileptiform discharges in hippocampal slice cultures. J Neurosci 25:4260–4269
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 22:211–216
Manikonda PK, Rajendra P, Devendranath D, Gunasekaran B, Channakeshava ARS, Sashidhar RB, Subramanyam C (2007) Influence of extremely low frequency magnetic fields on Ca2+ signaling and NMDA receptor functions in rat hippocampus. Neurosci Lett 413:145–149
Manna SS, Umathe SN (2012) Involvement of transient receptor potential vanilloid type 1 channels in the pro-convulsant effect of anandamide in pentylenetetrazole-induced seizures. Epilepsy Res 100:113–124
Meldrum BS (2002) Concept of activity-induced cell death in epilepsy: historical and contemporary perspectives. Prog Brain Res 135:3–11
Melnikova VO, Ananthaswamy HN (2005) Cellular and molecular events leading to the development of skin cancer. Mutat Res 571:91–106
Nazıroğlu M (2009) Role of selenium on calcium signaling and oxidative stress-induced molecular pathways in epilepsy. Neurochem Res 34:2181–2191
Nazıroğlu M (2012) Molecular role of catalase on oxidative stress-induced Ca(2+) signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct Res 32:134–141
Nazıroğlu M, Akman H. (2014) Effects of cellular phone and Wi-Fi-induced electromagnetic radiation on oxidative stress and molecular pathways in brain. I. Laher (ed.), Systems Biology of Free Radicals and Anti-Oxidants. Springer-Verlag Berlin Heidelberg DOI 10.1007/978-3-642-30018-9_210
Nazıroğlu M, Gümral N (2009) Modulator effects of L-carnitine and selenium on wireless devices (2.45 GHz)-induced oxidative stress and electroencephalography records in brain of rat. Int J Radiat Biol 85:680–689
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 32:290–297
Nazıroğlu M, Çelik Ö, Özgül C, Doğan S, Bal R, Gümral N, Rodríguez AB, Pariente JA (2012b) Melatonin modulates wireless devices (2.45 GHz)-induced brain and dorsal root ganglion injury through TRPM2 and voltage gated calcium channels in rat. Physiol Behav 105:683–692
Nazıroğlu M, Ciğ B, Doğan S, Uğuz AC, Dilek S, Faouzi D (2012c) 2.45-GHz wireless devices induce oxidative stress and proliferation through cytosolic Ca2+ influx in human leukemia cancer cells. Int J Radiat Biol 88:449–456
Nazıroğlu M, Dikici DM, Dursun S (2012d) Role of oxidative stress and Ca(2+) signaling on molecular pathways of neuropathic pain in diabetes: Focus on TRP channels. Neurochem Res 37:2065–2075
Nazıroğlu M, Çiğ B, Özgül C (2013a) Neuroprotection induced by N-acetylcysteine against cytosolic glutathione depletion induced-Ca2+ influx in dorsal root ganglion neurons of mice: Role of TRPV1 channels. Neuroscience 242:151–160
Nazıroğlu M, Akay MB, Celik O, Yıldırım MI, Balcı E, Yürekli VA (2013b) Capparis ovata Modulates Brain Oxidative Toxicity and Epileptic Seizures in Pentylentetrazol-Induced Epileptic Rats. Neurochem Res 38:780–788
Nazıroğlu M, Ciğ B, Ozgül C (2014) Modulation of oxidative stress and Ca(2+) mobilization through TRPM2 channels in rat dorsal root ganglion neuron by Hypericum perforatum. Neuroscience 28(263):27–35
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 27(5):e11828
Piacentini R, Ripoli C, Mezzogori D, Azzena GB, Grassi C (2008) Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity. J Cell Physiol 215:129–139
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
Salford LG, Nittby H, Brun A, Grafström G, Eberhardt JL, Malmgren L, Persson BRR (2007) Non-Thermal effects of EMF upon the mammalian brain: The lund experience. Environmentalist 27:493–500
Senol N, Nazıroğlu M, Yürüker V (2014) N-acetylcysteine and selenium modulate oxidative stress, antioxidant vitamin and cytokine values in traumatic brain injury-induced rats. Neurochem Res 39:685–692
Sun FJ, Guo W, Zheng DH, Zhang CQ, Li S, Liu SY, Yin Q, Yang H, Shu HF (2013) Increased expression of TRPV1 in the cortex and hippocampus from patients with mesial temporal lobe epilepsy. J Mol Neurosci 49:182–193
Susankova K, Tousova K, Vyklicky L, Teisinger J, Vlachova V (2006) Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1) current. Mol Pharmacol 70:383–394
Tjiattas L, Ortiz DO, Dhivant S, Mitton K, Rogers E, Shea TB (2004) Folate deficiency and homocysteine induce toxicity in cultured dorsal root ganglion neurons via cytosolic calcium accumulation. Aging Cell 3:71–76
Uğuz AC, Nazıroğlu M (2012) Effects of selenium on calcium signaling and apoptosis in rat dorsal root ganglion neurons induced by oxidative stress. Neurochem Res 37:1631–1638
Uğuz AC, Nazıroğlu M, Espino J, Bejarano I, González D, Rodríguez AB, Pariente JA (2009) Selenium modulates oxidative stress-induced cell apoptosis in human myeloid HL-60 cells via regulation of caspase-3,−9 and calcium influx. J Membr Biol 232:15–23
Uğuz AC, Cig B, Espino J, Bejarano I, Nazıroğlu M, Rodríguez AB, Pariente JA (2012) Melatonin potentiates chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor cells. J Pineal Res 53:91–98
Yang XS, He GL, Hao YT, Xiao Y, Chen CH, Zhang GB, Yu ZP (2012) Exposure to 2.45 GHz electromagnetic fields elicits an HSP-related stress response in rat hippocampus. Brain Res Bull 88:371–378
Zhao R, Zhang S, Xu Z, Ju L, Lu D, Yao G (2007) Studying gene expression profile of rat neuron exposed to 1800MHz radiofrequency electromagnetic fields with cDNA microassay. Toxicology 25(235):167–175
Zhou XR, Yuan HP, Qu W, Ma CY, Li HY, Wang Y (2008) The study of retinal ganglion cell apoptosis induced by different intensities of microwave irradiation. Ophthalmologica 222:6–10
Acknowledgments
Dr. Vahid Ghazizadeh was partially supported for the project by Free Oxygen Radical Society, Isparta, Turkey. Abstract of the manuscript submitted in 11th National Neuroscience Congress, April, 2013, Izmir, Turkey. The authors wish thanks to Dr. Peter Butterworth (King’s College London, UK) for revision of English of the manuscript. Authors’ roles: MN formulated the present hypothesis and was responsible for writing the report. VG were responsible for the analyses.
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The authors declare that they have no conflict of interest. All authors approved the final manuscript.
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Ghazizadeh, V., Nazıroğlu, M. 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, 787–799 (2014). https://doi.org/10.1007/s11011-014-9549-9
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DOI: https://doi.org/10.1007/s11011-014-9549-9