Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: the role of the endocannabinoid system.
Repetitive transcranial magnetic stimulation (rTMS) to treat depression has been thoroughly investigated in recent years. However, the underlying mechanisms are not fully understood. In this study, a chronic unpredictable mild stress (CUMS) paradigm was applied to male Sprague Dawley rats. Then rTMS was performed for 7 consecutive days, and the anti-depressive effects were evaluated by the sucrose preference test (SPT), the forced swimming test (FST), and the open-field test (OFT). Hippocampal cannabinoid type I receptor (CB1) expression was measured, and the expression levels of brain-derived neurotrophic factor (BDNF), Bcl-2, and Bax and the number of bromodeoxyuridine (BrdU)-positive cells were also investigated. These parameters were also observed after the selective CB1 receptor antagonist AM251 was used as a blocking agent. The results showed that CUMS induced a significant decrease in sucrose preference, a significant increase in immobility time in the FST, and a significantly decreased horizontal distance in the OFT. In addition, reduced hippocampal CB1 receptor, BDNF, and Bcl-2/Bax protein expression levels in CUMS rats, as well as decreased cell proliferation were also observed in the dentate gyrus. Meanwhile, rTMS treatment up-regulated cell proliferation; elevated CB1 receptor, BDNF, and Bcl-2/Bax expression levels in the hippocampus; and ameliorated depressive-like behaviors. All of these beneficial effects were abolished by AM251. These results indicate that rTMS increases BDNF production and hippocampal cell proliferation to protect against CUMS-induced changes through its effect on CB1 receptors.
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China.
Hua-ning
HN
Wang
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China; Xi'an city mental health center, Xi'an, China.
Lei
L
Wang
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China.
Rui-guo
RG
Zhang
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China.
Yun-chun
YC
Chen
Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
Ling
L
Liu
Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
Fang
F
Gao
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Huang
H
Nie
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Wu-gang
WG
Hou
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: pengzhengwu1446@163.com.
Zheng-wu
ZW
Peng
Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, 17 Changle Road, Xi'an, Shaanxi 710032, China. Electronic address: tanqingr@fmmu.edu.cn.
Qingrong
Q
Tan
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000528:radiation effects; D003863:Depression / Q000473:pathology* / Q000628:therapy*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000528:radiation effects; D005518:Food Preferences / Q000187:drug effects / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013550:Swimming / Q000523:psychology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D019208:Brain-Derived Neurotrophic Factor; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D051028:bcl-2-Associated X Protein; C103505:AM 251; D001973:Bromodeoxyuridine
Cannabinoid type I receptor; Depression; Hippocampus; Repetitive transcranial magnetic stimulation