Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Ginseng on Calretinin Expression in Mouse Hippocampus Following Exposure to 835 MHz Radiofrequency

  • Aryal, Bijay (Department of Pharmacology, Dankook University College of Medicine) ;
  • Maskey, Dhiraj (Department of Anatomy, Dankook University College of Medicine) ;
  • Kim, Myeung-Ju (Department of Anatomy, Dankook University College of Medicine) ;
  • Yang, Jae-Won (Oscotec Research Institute, Oscotec Inc.) ;
  • Kim, Hyung-Gun (Department of Pharmacology, Dankook University College of Medicine)
  • Received : 2010.10.17
  • Accepted : 2011.02.14
  • Published : 2011.06.29
Download PDF
⟨ Previous Next ⟩

Abstract

Exponential rise in the use of mobile communication devices has generated health concerns due to radiofrequency (RF) exposure due to its close proximity to the head. Calcium binding proteins like calretinin regulate the levels of calcium ($Ca^{2+}$) which plays an important role in biological systems. Ginseng is known for maintaining equilibrium in the human body and may play a beneficial radioprotectant role against electromagnetic field (EMF) exposure. In the present study, we evaluated the radioprotective effects of red ginseng (RG) extract in a mouse model. Calretinin (CR) expression was measured using a free-floating immunohistochemical method in the hippocampus of mice after 835 MHz EMF exposure for 5 h/d for 5 d at specific absorption rate=1.6 W/kg for the different experimental groups. The control animals were treated with NaCl while the experimental animals received 10 mg/kg ginseng, or 30 mg/kg; EMF exposed mice were also treated with NaCl, 10 mg/kg ginseng (E10), or 30 mg/kg (E30). Decreases in CR immunoreactivity (IR) along with loss of CA1 and CA3 interneurons and infragranular cells were observed in the ENaCl group while such losses were not observed in the E10 and E30 groups. CR IR significantly increased in the RG-treated group compared to control and EMF-exposed groups treated with NaCl. The study demonstrates that RG extract can serve as a radioprotective agent that maintains $Ca^{2+}$ homeostasis and prevents neuronal loss in the brain hippocampal region caused by RF exposure.

Keywords

References

  1. Dubreuil D, Jay T, Edeline JM. Does head-only exposure to GSM-900 electromagnetic fields affect the performance of rats in spatial learning tasks? Behav Brain Res 2002;129:203-210. https://doi.org/10.1016/S0166-4328(01)00344-8
  2. Ahlbom A, Green A, Kheifets L, Savitz D, Swerdlow A; ICNIRP (International Commission for Non-Ionizing Radiation Protection) Standing Committee on Epidemiology. Epidemiology of health effects of radiofrequency exposure. Environ Health Perspect 2004;112:1741-1754. https://doi.org/10.1289/ehp.7306
  3. Manikonda PK, Rajendra P, Devendranath D, Gunasekaran B, Channakeshava, Aradhya RS, Sashidhar RB, Subramanyam C. Influence of extremely low frequency magnetic fields on Ca2+ signaling and NMDA receptor functions in rat hippocampus. Neurosci Lett 2007;413:145-149. https://doi.org/10.1016/j.neulet.2006.11.048
  4. Mausset AL, de Seze R, Montpeyroux F, Privat A. Effects of radiofrequency exposure on the GABAergic system in the rat cerebellum: clues from semi-quantitative immunohistochemistry. Brain Res 2001;912:33-46. https://doi.org/10.1016/S0006-8993(01)02599-9
  5. Salford LG, Brun AE, Eberhardt JL, Malmgren L, Persson BR. Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones. Environ Health Perspect 2003;111:881-883. https://doi.org/10.1289/ehp.6039
  6. Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A 2000;97:11032-11037. https://doi.org/10.1073/pnas.97.20.11032
  7. Eyre MD, Richter-Levin G, Avital A, Stewart MG. Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient. Eur J Neurosci 2003;17:1973-1980. https://doi.org/10.1046/j.1460-9568.2003.02624.x
  8. Sakatani S, Okada YC, Hirose A. A quantitative evaluation of dominant membrane potential in generation of magnetic field using a pyramidal cell model at hippocampus CA3. Neurocomputing 2002;44-46:153-160.
  9. Blackman CF. Calcium release from neural tissue: experimental results and possible mechanisms. In: Norden B, Ramel C, eds. Interaction mechanisms of low-level electromagnetic fields in living systems. Oxford: Oxford University Press, 1992. p.107-129.
  10. Bawin SM, Adey WR, Sabbot IM. Ionic factors in release of 45Ca2+ from chicken cerebral tissue by electromagnetic fields. Proc Natl Acad Sci U S A 1978;75:6314-6418. https://doi.org/10.1073/pnas.75.12.6314
  11. Adey WR, Bawin SM, Lawrence AF. Effects of weak amplitude-modulated microwave fields on calcium efflux from awake cat cerebral cortex. Bioelectromagnetics 1982;3:295-307. https://doi.org/10.1002/bem.2250030302
  12. Airaksinen MS, Eilers J, Garaschuk O, Thoenen H, Konnerth A, Meyer M. Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene. Proc Natl Acad Sci U S A 1997; 94:1488-1493. https://doi.org/10.1073/pnas.94.4.1488
  13. Blasco-Ibanez JM, Freund TF. Distribution, ultrastructure, and connectivity of calretinin-immunoreactive mossy cells of the mouse dentate gyrus. Hippocampus 1997;7: 307-320. https://doi.org/10.1002/(SICI)1098-1063(1997)7:3<307::AID-HIPO6>3.0.CO;2-H
  14. Liu Y, Fujise N, Kosaka T. Distribution of calretinin immunoreactivity in the mouse dentate gyrus. I. General description. Exp Brain Res 1996;108:389-403.
  15. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000;11:565-576. https://doi.org/10.1023/A:1008980200583
  16. Kitts DD, Wijewickreme AN, Hu C. Antioxidant properties of a North American ginseng extract. Mol Cell Biochem 2000;203:1-10. https://doi.org/10.1023/A:1007078414639
  17. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  18. Liu WK, Xu SX, Che CT. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci 2000;67:1297-1306. https://doi.org/10.1016/S0024-3205(00)00720-7
  19. Keum YS, Han SS, Chun KS, Park KK, Park JH, Lee SK, Surh YJ. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res 2003;523-524:75-85.
  20. Ben-Hur E, Fulder S. Effect of Panax ginseng saponins and Eleutherococcus senticosus on survival of cultured mammalian cells after ionizing radiation. Am J Chin Med 1981;9:48-56. https://doi.org/10.1142/S0192415X8100007X
  21. Ong YC, Yong EL. Panax (ginseng): panacea or placebo? Molecular and cellular basis of its pharmacological activity. Ann Acad Med Singapore 2000;29:42-46.
  22. Kim TH, Lee YS, Cho CK, Park S, Choi SY, Yool SY. Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes. Cancer Biother Radiopharm 1996;11:267-272. https://doi.org/10.1089/cbr.1996.11.267
  23. Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol 1999;55:567-575. https://doi.org/10.1007/s002280050674
  24. Song JY, Han SK, Bae KG, Lim DS, Son SJ, Jung IS, Yi SY, Yun YS. Radioprotective effects of ginsan, an immunomodulator. Radiat Res 2003;159:768-774. https://doi.org/10.1667/0033-7587(2003)159[0768:REOGAI]2.0.CO;2
  25. Zhang JS, Sigdestad CP, Gemmell MA, Grdina DJ. Modification of radiation response in mice by fractionated extracts of Panax ginseng. Radiat Res 1987;112:156-163. https://doi.org/10.2307/3577086
  26. Kim JY, Germolec DR, Luster MI. Panax ginseng as a potential immunomodulator: studies in mice. Immunopharmacol Immunotoxicol 1990;12:257-276. https://doi.org/10.3109/08923979009019672
  27. Liang CL, Sinton CM, Sonsalla PK, German DC. Midbrain dopaminergic neurons in the mouse that contain calbindin-D28k exhibit reduced vulnerability to MPTP-induced neurodegeneration. Neurodegeneration 1996;5:313-318. https://doi.org/10.1006/neur.1996.0042
  28. Maskey D, Kim M, Aryal B, Pradhan J, Choi IY, Park KS, Son T, Hong SY, Kim SB, Kim HG, et al. Effect of 835 MHz radiofrequency radiation exposure on calcium binding proteins in the hippocampus of the mouse brain. Brain Res 2010;1313:232-241. https://doi.org/10.1016/j.brainres.2009.11.079
  29. Roberts WM. Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells. J Neurosci 1994;14(5 Pt 2):3246-3262.
  30. Lenzi D, Roberts WM. Calcium signalling in hair cells: multiple roles in a compact cell. Curr Opin Neurobiol 1994;4:496-502. https://doi.org/10.1016/0959-4388(94)90049-3
  31. The cell phone and the cell: the role of calcium. Available from: http://www.thenhf.com/articles/articles_719/articles _719.htm.
  32. Gonzalez D, Satriotomo I, Miki T, Lee KY, Yokoyama T, Touge T, Matsumoto Y, Li HP, Kuriyama S, Takeuchi Y. Effects of monocular enucleation on calbindin-D 28k and c-Fos expression in the lateral geniculate nucleus in rats. Okajimas Folia Anat Jpn 2005;82:9-18. https://doi.org/10.2535/ofaj.82.9
  33. Lee TK, Allison RR, O'Brien KF, Khazanie PG, Johnke RM, Brown R, Bloch RM, Tate ML, Dobbs LJ, Kragel PJ. Ginseng reduces the micronuclei yield in lymphocytes after irradiation. Mutat Res 2004;557:75-84. https://doi.org/10.1016/j.mrgentox.2003.10.002
  34. Liao B, Newmark H, Zhou R. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol 2002;173:224-234. https://doi.org/10.1006/exnr.2001.7841
  35. Chen XC, Zhu YG, Zhu LA, Huang C, Chen Y, Chen LM, Fang F, Zhou YC, Zhao CH. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. Eur J Pharmacol 2003;473:1-7. https://doi.org/10.1016/S0014-2999(03)01945-9
  36. Lee E, Kim S, Chung KC, Choo MK, Kim DH, Nam G, Rhim H. 20(S)-ginsenoside $Rh_2$, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons. Eur J Pharmacol 2006;536:69-77. https://doi.org/10.1016/j.ejphar.2006.02.038
  37. Lee JH, Jeong SM, Kim JH, Lee BH, Yoon IS, Lee JH, Choi SH, Lee SM, Park YS, Lee JH et al. Effects of ginsenosides and their metabolites on voltage-dependent Ca(2+) channel subtypes. Mol Cells 2006;21:52-62.
  38. Rhim H, Kim H, Lee DY, Oh TH, Nah SY. Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate $Ca^{2+}$ channel currents in rat sensory neurons. Eur J Pharmacol 2002;436:151-158. https://doi.org/10.1016/S0014-2999(01)01613-2
  39. Zhang YF, Fan XJ, Li X, Peng LL, Wang GH, Ke KF, Jiang ZL. Ginsenoside Rg1 protects neurons from hypoxic-ischemic injury possibly by inhibiting $Ca^{2+}$ influx through NMDA receptors and L-type voltage-dependent $Ca^{2+}$ channels. Eur J Pharmacol 2008;586:90-99. https://doi.org/10.1016/j.ejphar.2007.12.037
  40. Liu M, Zhang JT. Protective effects of ginsenoside Rb1 and Rg1 on cultured hippocampal neurons. Yao Xue Xue Bao 1995;30:674-678.
  41. Kim S, Ahn K, Oh TH, Nah SY, Rhim H. Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 2002;296:247-254. https://doi.org/10.1016/S0006-291X(02)00870-7
  42. Bas O, Odaci E, Kaplan S, Acer N, Ucok K, Colakoglu S. 900 MHz electromagnetic field exposure affects qualitative and quantitative features of hippocampal pyramidal cells in the adult female rat. Brain Res 2009;1265:178-185. https://doi.org/10.1016/j.brainres.2009.02.011
  43. Bas O, Odaci E, Mollaoglu H, Ucok K, Kaplan S. Chronic prenatal exposure to the 900 megahertz electromagnetic field induces pyramidal cell loss in the hippocampus of newborn rats. Toxicol Ind Health 2009;25:377-384. https://doi.org/10.1177/0748233709106442
  44. Odaci E, Bas O, Kaplan S. Effects of prenatal exposure to a 900 MHz electromagnetic field on the dentate gyrus of rats: a stereological and histopathological study. Brain Res 2008;1238:224-229. https://doi.org/10.1016/j.brainres.2008.08.013
  45. Jenrow KA, Ratkewicz AE, Lemke NW, Kadiyala M, Zalinski DN, Burdette DE, Elisevich KV. Effects of kindling and irradiation on neuronal density in the rat dentate gyrus. Neurosci Lett 2004;371:45-50. https://doi.org/10.1016/j.neulet.2004.08.036
  46. Teyler TJ, DiScenna P. The topological anatomy of the hippocampus: a clue to its function. Brain Res Bull 1984;12:711-719. https://doi.org/10.1016/0361-9230(84)90152-7
  47. Barbas H, Blatt GJ. Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus 1995;5:511-533. https://doi.org/10.1002/hipo.450050604

Cited by

  1. The world ginseng market and the ginseng (Korea) vol.37, pp.1, 2011, https://doi.org/10.5142/jgr.2013.37.1