Pulsed electromagnetic field attenuated PTSD-induced failure of conditioned fear extinction

Document Type: Original Article

Authors

1 School of Biology, Damghan University, Damghan, Semnan, Iran

2 Department of Medical Physics, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

Abstract

Objective(s): This study aimed to determine whether exposure to pulsed electromagnetic field (PEMF) can impair behavioral failure as induced by PTSD, and also its possible effects on hippocampal neurogenesis. PEMF was used as a non-invasive therapeutic tool in psychiatry.
Materials and Methods: Male rats were divided into Control-Sham exposed, Control-PEMF, PTSD-Sham exposed, and PTSD-PEMF groups. PTSD rats were conducted by the single prolonged stress procedures and then conditioned by the contextual fear conditioning apparatus. Control rats were only conditioned. Experimental rats were submitted to daily PEMF (7 mT, 30 Hz for 16 min/day, 14 days). Sham-exposed groups were submitted to the turned off PEMF apparatus. Fear extinction, sensitized fear and anxiety, cell density in the hippocampus, and proliferation and survival rate of BrdU-labeled cells were evaluated.
Results: Freezing of PTSD-PEMF rats was significantly lower than PTSD-Sham exposed. In the PTSD-PEMF, center and total crossing in open field, also the percentage of open arms entry and time in the elevated plus maze, significantly increased as compared with PTSD-Sham exposed (P<0.001). Numbers of CA1, CA3, and DG cells in PTSD-PEMF and Control-Sham exposed groups were significantly more than PTSD-Sham exposed (P<0.001). There were more BrdU-positive cells in the DG of the PTSD-PEMF as compared with the PTSD-Sham exposed. Qualitative observations showed an increased number of surviving BrdU-positive cells in the PTSD-PEMF as compared with PTSD-Sham exposed.
Conclusion: Using 14-day PEM attenuates the PTSD-induced failure of conditioned fear extinction and exaggerated sensitized fear, and this might be related to the neuroprotective effects of magnetic fields on the hippocampus.

Keywords

Main Subjects


1. Bisson JI, Cosgrove S, Lewis C, Robert NP. Post-traumatic stress disorder. BMJ 2015; 351:h6161.
2. Wessa M, Flor H. Failure of extinction of fear responses in posttraumatic stress disorder: evidence from second-order conditioning. Am J Psychiatry 2007; 164:1684-1692.
3. Blechert J, Michael T, Vriends N, Margraf J, Wilhelm FH. Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. Behav Res Ther 2007; 45:2019-2033.
4. Liberzon I, Sripada CS. The functional neuroanatomy of PTSD: a critical review. Prog Brain Res 2008; 167:151-169.
5. Kuhlmann S, Piel M, Wolf OT. Impaired memory retrieval after psychosocial stress in healthy young men. J Neurosci 2005; 25:2977-2982.
6. Czeh B, Welt T, Fischer AK, Erhardt A, Schmitt W, Muller MB, et al. Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: effects on stress hormone levels and adult hippocampal neurogenesis. Biol Psychiatry 2002; 52:1057-1065.
7. Acheson DT, Gresack JE, Risbrough VB. Hippocampal dysfunction effects on context memory: possible etiology for post-traumatic stress disorder. Neuropharmacology 2012; 62:674-685.
8. Bremner JD, Elzinga B, Schmahl C, Vermetten E. Structural and functional plasticity of the human brain in posttraumatic stress disorder. Prog Brain Res. 2008;167:171-186.
9. Noohi S, Amirsalari S. History, studies and specific uses of repetitive transcranial magnetic stimulation (rTMS) in treating epilepsy. Iran J Child Neurol 2016; 10:1-8.
10. J. RP. Bioelectromagnetic and Subtle Energy Medicine. Ann N Y Acad Sci. 2009;1172:297-311.
11. Ma F, Li W, Li X, Tran Ba H, Suguro R, Guan R, et al. Novel protective effects of pulsed electromagnetic field ischemia/reperfusion injury rats. Biosci Rep 2016; 36:e00420.
12. Ueyama E, Ukai S, Ogawa A, Yamamoto M, Kawaguchi S, Ishii R, et al. Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats. Psychiatry Clin Neurosci 2011; 65:77-81.
13. Piacentini R, Ripoli C, Mezzogori D, Azzena GB, Grassi C. Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Ca(v)1-channel activity. J Cell Physiol 2008; 215:129-139.
14. Cuccurazzu B, Leone L, Podda MV, Piacentini R, Riccardi E, Ripoli C, et al. Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol 2010; 226:173-182.
15. Wang JW, David DJ, Monckton JE, Battaglia F, Hen R. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci 2008;28:1374-1384.
16. Zhen J, Qian Y, Fu J, Su R, An H, Wang W, et al. Deep brain magnetic stimulation promotes neurogenesis and restores cholinergic activity in a transgenic mouse model of Alzheimer’s disease. Front in Neural Circuits 2017; 30:11:48.
17. Mirshekar M, Abrari K, Goudarzi I, Rashidy-Pour A. Systemic administrations of beta-estradiol alleviate both conditioned and sensitized fear responses in an ovariectomized rat model of post-traumatic stress disorder. Neurobiol Learn Mem 2013; 102:12-19.
18. Liberzon I, Krstov M, Young EA. Stress-restress: effects on ACTH and fast feedback. Psychoneuroendocrinology 1997; 22:443-453.
19. Liberzon I, Lopez JF, Flagel SB, Vazquez DM, Young EA. Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder. J Neuroendocrinol 1999; 11:11-17.
20. Zarrindast MR, Taheri S, Rezayof A. The effects of histaminergic agents in the nucleus accumbens of rats in the elevated plus-maze test of anxiety. Iran J Psychiatry 2010; 5:11-17.
21. Abbasnia K, Ghanbari A, Abedian M, Ghanbari A, Sharififar S, Azari H. The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells. Anat Cell Biol 2015; 48:104-113.
22. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. 2008; 6th Edition, Churchill Livingstone, Elsevier, China.
23. Alijan-pour J, Abrari K, Lashkar bluki T, Ghorbanian MT, Goudarzi I, Elahdadi Salmani M. Ethanol disrupts reactivated contextual conditioned fear memory: behavioral and histological perspectives. Cell J 2012; 13:265-274.
24. Haji Ghasem Kashani M, Ghorbanian MT, Hosseinpour L. Transplantation of deprenyl-induced tyrosine hydroxylase-positive cells improves 6-OHDA-lesion rat model of parkinson’s disease: behavioral immunohistochemical and evaluation. Cell J 2013; 15:55-64.
25. Rostami A, Shahani M, Zarrindast MR, Semnanian S, Rahmati Roudsari M, Rezaei Tavirani M, et al. Effects of 3 Hz and 60 Hz extremely low frequency electromagnetic fields on anxiety-like behaviors, memory retention of passive avoidance and electrophysiological properties of male rats. J Lasers Med Sci 2016; 7:120-125.
26. Sakhnini L, Al-Ghareeb S, Khalil S, Ahmed R, Abdul Ameer A, Kamal A. Effects of exposure to 50 Hz electromagnetic fields on Morris water-maze performance of prenatal and neonatal mice. J Assoc Arab Uni Basic Appl Sci 2013; 15:1–6
27. Kim SC, Jo YS, Kim IH, Kim H, Choi JS. Lack of medial prefrontal cortex activation underlies the immediate extinction deficit. J Neurosci 2010; 30:832-837.
28. Baek K, Chae JH, Jeong J. The effect of repetitive transcranial magnetic stimulation on fear extinction in rats. Neuroscience 2012; 200:159-165.
29. Fard MT, Bahaeddini A, Shomali T, Haghighi SK. Effect of extremely low frequency electromagnetic field and/or GABAB receptors on foot shock-induced aggression in rats. Basic Clin Neurosci 2014; 5:169-172.
30. Guo F, Lou J, Han X, Deng Y, Huang X. Repetitive transcranial magnetic stimulation ameliorates cognitive impairment by enhancing neurogenesis and suppressing apoptosis in the hippocampus in rats with ischemic stroke. Front Physiol 2017; 8:559.
31. Scott BW, Wojtowicz JM, Burnham WM. Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures. Exp Neurol 2000; 165:231-236.
32. Müller MB, Toschi N, Kresse AE, Post A, Keck ME. Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain. Neuropsychopharmacology 2000; 23:205-215.
33. Vithlani M, Hines RM, Zhong P, Terunuma M, Hines DJ, Revilla-Sanchez R, et al. The ability of BDNF to modify neurogenesis and depressive-like behaviors is dependent upon phosphorylation of tyrosine residues 365/367 in the GABA(A)-receptor γ2 subunit. J Neurosci 2013; 33:15567-15577.
34. Bath KG, Akins MR, Lee FS. BDNF control of adult SVZ neurogenesis. Dev Psychobiol 2012; 54:578-589.
35. Lee J, Duan W, Long JM, Ingram DK, Mattson MP. Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 2000; 15:99-108.
36. Gedge L, Beaudoin A, Lazowski L, du Toit R, Jokic R, Milev R. Effects of electroconvulsive therapy and repetitive transcranial magnetic stimulation on serum brain-derived neurotrophic factor levels in patients with depression. Front Psychiatry 2012; 3:12.
37. Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Hayashi K, Katsuki A, et al. [Blood levels of brain-derived neurotrophic factor (BDNF) in major depressive disorder]. Seishin Shinkeigaku Zasshi 2010; 112:982-985.
38. Wang HY, Crupi D, Liu J, Stucky A, Cruciata G, Di Rocco A, et al. Repetitive transcranial magnetic stimulation enhances BDNF-TrkB signaling in both brain and lymphocyte. J Neurosci 2011; 31:11044-11054.
39. Tasset I, Medina FJ, Jimena I, Aguera E, Gascon F, Feijoo M, et al. Neuroprotective effects of extremely low-frequency electromagnetic fields on a Huntington’s disease rat model: effects on neurotrophic factors and neuronal density. Neuroscience 2012; 209:54-63.
40. Túnez I, Montilla P, Muñoz MdC, Medina FJ, Drucker-Colín R. Effect of transcranial magnetic stimulation on oxidative stress induced by 3-nitropropionic acid in cortical synaptosomes. Neurosci Res 2006; 56:91-95.
41. Yoon KJ, Lee Y-T, Chung P-W, Lee YK, Kim DY, Chun MH. Effects of repetitive transcranial magnetic stimulation on behavioral recovery during early stage of traumatic brain injury in rats. J Korean Med Sci 2015; 30:1496-1502.
42. Perusini JN, Meyer EM, Long VA, Rau V, Nocera N, Avershal J, et al. Induction and expression of fear sensitization caused by acute traumatic stress. Neuropsychopharmacology 2016; 41:45-57.
43. Wang W, Liu Y, Zheng H, Wang HN, Jin X, Chen YC, et al. A modified single-prolonged stress model for post-traumatic stress disorder. Neurosci Lett 2008; 441:237-241.
44. Choleris E, Thomas AW, Kavaliers M, Prato FS. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neurosci Biobehav Rev 2001; 25:235-260.
45. Wang Hn, Bai Yh, Chen Yc, Zhang Rg, Wang Hh, Zhang Yh, et al. Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder. PLoS One 2015; 10:e0117189.
46. White D, Tavakoli S. Repetitive transcranial magnetic stimulation for treatment of major depressive disorder with comorbid generalized anxiety disorder. Ann Clin Psychiatry 2015; 27:192-196.
47. Paes F, Baczynski T, Novaes F, Marinho T, Arias-Carrión O, Budde H, et al. Repetitive transcranial magnetic stimulation (rTMS) to treat social anxiety disorder: Case reports and a review of the literature. Clin Pract Epidemiol Ment Health 2013; 9:180-188.
48. Hargreaves GA, McGregor IS, Sachdev PS. Chronic repetitive transcranial magnetic stimulation is anti-depressant but not anxiolytic in rat models of anxiety and depression. Psychiatry Res 2005; 137:113-121.