In vitro developmental neurotoxicity following chronic exposure to 50 Hz extremely low-frequency electromagnetic fields in primary rat cortical cultures

Toxicological Sciences

Volumn 149, Issue 2, 2016, Pages 433-440

  De Groot, Martje W G D M ^a   Van Kleef, Regina G D M ^a   De Groot, Aart ^a   Westerink, Remco H S ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

Author keywords

Extremely low frequency electromagnetic fields (ELF EMF); In vitro developmental neurotoxicity (DNT); Multielectrode arrays (MEA); Neurite outgrowth; Primary rat cortical cultures; Single cell fluorescent microscopy

Indexed keywords

BETA TUBULIN; GLUTAMIC ACID; CALCIUM;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN CELL; BRAIN CELL CULTURE; CALCIUM CELL LEVEL; CALCIUM HOMEOSTASIS; CALCIUM SIGNALING; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DEPOLARIZATION; ELECTRIC ACTIVITY; ELECTROMAGNETIC FIELD; EXTREMELY LOW FREQUENCY ELECTROMAGNETIC FIELD; FEMALE; FLUORESCENCE MICROSCOPY; IMMUNOFLUORESCENCE TEST; IN VITRO STUDY; LONG TERM EXPOSURE; NERVE CELL DIFFERENTIATION; NERVE FIBER GROWTH; NEUROTOXICITY; NONHUMAN; RAT; ANIMAL; BRAIN CORTEX; CELL CULTURE; CELL SURVIVAL; ELECTROMAGNETISM; METABOLISM; NERVE CELL; NEURITE; RADIATION RESPONSE; WISTAR RAT;

ANIMALS; CALCIUM; CELL SURVIVAL; CELLS, CULTURED; CEREBRAL CORTEX; ELECTROMAGNETIC FIELDS; NEURITES; NEURONS; RATS; RATS, WISTAR;

EID: 84960080251     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfv242     Document Type: Article

References (57)

1. Ahlbom, I. C., Cardis, E., Green, A., Linet, M., Savitz, D., Swerdlow, A., and ICNIRP (International Commission for Non-Ionizing Radiation Protection) Standing Committee on Epidemiology. (2001). Review of the epidemiologic literature on EMF and Health. Environ. Health Perspect. 109(Suppl 6), 911-933.
2. Arie, Y., Iketani, M., Takamatsu, K., Mikoshiba, K., Goshima, Y., and Takei, K. (2009). Developmental changes in the regulation of calcium-dependent neurite outgrowth. Biochem. Biophys. Res. Commun. 379, 11-15.
3. Bal-Price, A. K., Hogberg, H. T., Buzanska, L., Lenas, P., van Vliet, E., and Hartung, T. (2010). In vitro developmental neurotoxicity (DNT) testing: relevant models and endpoints. Neurotoxicology 31, 545-554.
4. Barclay, J. W., Morgan, A., and Burgoyne, R. D. (2005). Calciumdependent regulation of exocytosis. Cell Calcium 38, 343-353.
5. Berridge, M., Lipp, P., and Bootman, M. (1999). Calcium signalling. Curr. Biol. 9, R157-R159.
6. Blackman, C. F., Benane, S. G., House, D. E., and Pollock, M. M. (1993). Action of 50 Hz magnetic fields on neurite outgrowth in pheochromocytoma cells. Bioelectromagnetics 14, 273-286.
7. Briz, V., Galofre, M., and Sunol, C. (2010). Reduction of glutamatergic neurotransmission by prolonged exposure to dieldrin involves NMDA receptor internalization and metabotropic glutamate receptor 5 downregulation. Toxicol. Sci. 113, 138-149.
8. Bunch, K. J., Keegan, T. J., Swanson, J., Vincent, T. J., and Murphy, M. F. (2014). Residential distance at birth from overhead high-voltage powerlines: childhood cancer risk in Britain 1962-2008. Br. J. Cancer 110, 1402-1408.
9. Butz, M., Worgotter, F., and van Ooyen, A. (2009). Activitydependent structural plasticity. Brain Res. Rev. 60, 287-305.
10. Clancy, B., Finlay, B. L., Darlington, R. B., and Anand, K. J. (2007). Extrapolating brain development from experimental species to humans. Neurotoxicology 28, 931-937.
11. Clapham, D. E. (2007). Calcium signaling. Cell 131, 1047-1058.
12. Croom, E. L., Shafer, T. J., Evans, M. V., Mundy, W. R., Eklund, C. R., Johnstone, A. F., Mack, C. M., and Pegram, R. A. (2015). Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: a case study of lindane-induced neurotoxicity. Toxicol. Appl. Pharmacol. 283, 9-19.
13. de Groot, M. W., Dingemans, M. M., Rus, K. H., de Groot, A., and Westerink, R. H. (2014a). Characterization of calcium responses and electrical activity in differentiating mouse neural progenitor cells in vitro. Toxicol. Sci. 137, 428-435.
14. de Groot, M. W., Kock, M. D., and Westerink, R. H. (2014b). Assessment of the neurotoxic potential of exposure to 50 Hz extremely low frequency electromagnetic fields (ELF-EMF) in naive and chemically stressed PC12 cells. Neurotoxicology 44, 358-364.
15. de Groot, M. W., Westerink, R. H., and Dingemans, M. M. (2013). Don't judge a neuron only by its cover: neuronal function in in vitro developmental neurotoxicity testing. Toxicol. Sci. 132, 1-7.
16. Defranchi, E., Novellino, A., Whelan, M., Vogel, S., Ramirez, T., van Ravenzwaay, B., and Landsiedel, R. (2011). Feasibility assessment of micro-electrode chip assay as a method of detecting neurotoxicity in vitro. Front. Neuroeng. 4, 6.
17. Fellin, T. (2009). Communication between neurons and astrocytes: relevance to the modulation of synaptic and network activity. J. Neurochem. 108, 533-544.
18. Feychting, M., Ahlbom, A., and Kheifets, L. (2005). EMF and health. Annu. Rev. Public Health 26, 165-189.
19. Gomez, T. M., and Zheng, J. Q. (2006). The molecular basis for calcium-dependent axon pathfinding. Nat. Rev. Neurosci. 7, 115-125.
20. Greenland, S., Sheppard, A. R., Kaune, W. T., Poole, C., and Kelsh, M. A. (2000). A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group. Epidemiology 11, 624-634.
21. Grynkiewicz, G., Poenie, M., and Tsien, R. Y. (1985). A new generation of Ca2+ indicators with greatly improved fluorescence properties. J. Biol. Chem. 260, 3440-3450.
22. Hausherr, V., van Thriel, C., Krug, A., Leist, M., and Schobel, N. (2014). Impairment of glutamate signaling in mouse central nervous system neurons in vitro by tri-ortho-cresyl phosphate at noncytotoxic concentrations. Toxicol. Sci. 142, 274-284.
23. Heusinkveld, H. J., Molendijk, J., van den Berg, M., and Westerink, R. H. (2013). Azole fungicides disturb intracellular Ca2+ in an additive manner in dopaminergic PC12 cells. Toxicol. Sci. 134, 374-381.
24. Hogberg, H. T., Sobanski, T., Novellino, A., Whelan, M., Weiss, D. G., and Bal-Price, A. K. (2011). Application ofmicro-electrode arrays (MEAs) as an emerging technology for developmental neurotoxicity: evaluation of domoic acid-induced effects in primary cultures of rat cortical neurons. Neurotoxicology 32, 158-168.
25. IARC Working Group (2002). IARC Monographs on the evaluation of carcinogenic risks to humans. Volume 80: Non-Ionizing Radiation, Part 1: Static and Extremely Low-Frequency (ELF) Electric and Magnetic Fields. http://monographs.iarc.fr/ENG/Monographs/Vol14902/mono80.pdf,Accessed December 1, 2015.
26. International Commission on Non-Ionizing Radiation Protection. (2010). Guidelines for limiting exposure to timevarying electric and magnetic fields (1Hz to 100 kHz). Health Phys. 99, 818-836.
27. Johnstone, A. F., Gross, G. W., Weiss, D. G., Schroeder, O. H., Gramowski, A., and Shafer, T. J. (2010). Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology. 31, 331-350.
28. Kheifets, L., Ahlbom, A., Crespi, C. M., Draper, G., Hagihara, J., Lowenthal, R. M., Mezei, G., Oksuzyan, S., Schuz, J., Swanson, J., et al. (2010). Pooled analysis of recent studies on magnetic fields and childhood leukaemia. Br. J. Cancer 103, 1128-1135.
29. Kraft, A. D. (2015). The use of glial data in human health assessments of environmental contaminants. Toxicology 333, 127-136.
30. Leclerc, C., Neant, I., and Moreau, M. (2011). Early neural development in vertebrates is also a matter of calcium. Biochimie 93, 2102-2111.
31. Lefew, W. R., McConnell, E. R., Crooks, J. L., and Shafer, T. J. (2013). Evaluation of microelectrode array data using Bayesian modeling as an approach to screening and prioritization for neurotoxicity testing. Neurotoxicology 36, 34-41.
32. Luo, F. L., Yang, N., He, C., Li, H. L., Li, C., Chen, F., Xiong, J. X., Hu, Z. A., and Zhang, J. (2014). Exposure to extremely low frequency electromagnetic fields alters the calcium dynamics of cultured entorhinal cortex neurons. Environ. Res. 135, 236-246.
33. Mack, C. M., Lin, B. J., Turner, J. D., Johnstone, A. F., Burgoon, L. D., and Shafer, T. J. (2014). Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes. Neurotoxicology 40, 75-85.
34. Mattson, M. P. and Kater, S. B. (1987). Calcium regulation of neurite elongation and growth cone motility. J. Neurosci. 7, 4034-4043.
35. McConnell, E. R., McClain, M. A., Ross, J., Lefew, W. R., and Shafer, T. J. (2012). Evaluation of multi-well microelectrode arrays for neurotoxicity screening using a chemical training set. Neurotoxicology 33, 1048-1057.
36. McFarlane, E. H., Dawe, G. S., Marks, M., and Campbell, I. C. (2000). Changes in neurite outgrowth but not in cell division induced by low EMF exposure: influence of field strength and culture conditions on responses in rat PC12 pheochromocytoma cells. Bioelectrochemistry 52, 23-28.
37. Meijer, M., Brandsema, J. A. R., Nieuwenhuis, D., Wijnolts, F. M. J., Dingemans, M. M. L., and Westerink, R. H. S. (2015). Inhibition of voltage-gated calcium channels after subchronic and repeated exposure of PC12 cells to different classes of insecticides. Toxicol. Sci. 147, 607-617.
38. Miller, G. W. (2014). Improving reproducibility in toxicology. Toxicol. Sci. 139, 1-3.
39. Morabito, C., Guarnieri, S., Fano, G., and Mariggio, M. A. (2010). Effects of acute and chronic low frequency electromagnetic field exposure on PC12 cells during neuronal differentiation. Cell. Physiol. Biochem. 26, 947-958.
40. Neher, E., and Sakaba, T. (2008). Multiple roles of calcium ions in the regulation of neurotransmitter release. Neuron 59, 861-872.
41. Nicolas, J., Hendriksen, P. J., van Kleef, R. G., de Groot, A., Bovee, T. F., Rietjens, I. M., and Westerink, R. H. (2014). Detection of marine neurotoxins in food safety testing using a multielectrode array. Mol. Nutr. Food Res. 58, 2369-2378.
42. Otto, M., and von Muhlendahl, K. E. (2007). Electromagnetic fields (EMF): do they play a role in children's environmental health (CEH)? Int. J. Hyg. Environ. Health 210, 635-644.
43. Pall, M. L. (2013). Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J. Cell. Mol. Med. 17, 958-965.
44. Piacentini, R., Ripoli, C., Mezzogori, D., Azzena, G. B., and 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.
45. Rice, D., and Barone, S. Jr. (2000). Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ. Health Perspect. 108(Suppl 3), 511-533.
46. Robinette, B. L., Harrill, J. A., Mundy, W. R., and Shafer, T. J. (2011). In vitro assessment of developmental neurotoxicity: use of microelectrode arrays to measure functional changes in neuronal network ontogeny. Front. Neuroeng. 4, 1-9.
47. Rusanescu, G., Qi, H., Thomas, S. M., Brugge, J. S., and Halegoua, S. (1995). Calcium influx induces neurite growth through a Src-Ras signaling cassette. Neuron 15, 1415-1425.
48. Tang, F., Dent, E. W., and Kalil, K. (2003). Spontaneous calcium transients in developing cortical neurons regulate axon outgrowth. J. Neurosci. 23, 927-936.
49. Valdivia, P., Martin, M., LeFew, W. R., Ross, J., Houck, K. A., and Shafer, T. J. (2014). Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds. Neurotoxicology 44, 204-217.
50. Vallotton, P., Lagerstrom, R., Sun, C., Buckley, M., Wang, D., De Silva, M., Tan, S. S., and Gunnersen, J. M. (2007). Automated analysis of neurite branching in cultured cortical neurons using HCA-Vision. Cytometry A. 71, 889-895.
51. van Ooyen, A. (1994). Activity-dependent neural network development. Network: Comput. Neural Syst. 5, 401-423.
52. Wallace, K., Strickland, J. D., Valdivia, P., Mundy, W. R., and Shafer, T. J. (2015). A multiplexed assay for determination of neurotoxicant effects on spontaneous network activity and viability from microelectrode arrays. Neurotoxicology 49, 79-85.
53. Wang, D., Lagerstrom, R., Sun, C., Bishof, L., Valotton, P., and Gotte, M. (2010). HCA-vision: automated neurite outgrowth analysis. J. Biomol. Screen. 15, 1165-1170.
54. Westerink, R. H. (2006). Targeting exocytosis: ins and outs of the modulation of quantal dopamine release. CNS Neurol. Disord. Drug Targets 5, 57-77.
55. Westerink, R. H. (2013). Do we really want to REACH out to in vitro? Neurotoxicology 39, 169-172.
56. World Health Organization (2007). Electromagnetic fields and public health. Exposure to extremely low frequency fields. Fact sheet 322: http://www.who.int/peh-emf/publications/facts/fs322/en/Accessed December 1, 2015.
57. Zhang, Y., Ding, J., Duan, W., and Fan, W. (2005). Influence of pulsed electromagnetic field with different pulse duty cycles on neurite outgrowth in PC12 rat pheochromocytoma cells. Bioelectromagnetics 26, 406-411.