高频重复经颅磁刺激通过调节内源性大麻素信号传导来调节小鼠海马体和前额叶皮质的神经振荡。

High-frequency repetitive transcranial magnetic stimulation regulates neural oscillations of the hippocampus and prefrontal cortex in mice by modulating endocannabinoid signalling.

作者信息

Peng Zheng-Wu, Zhou Cui-Hong, Xue Shan-Shan, Yu Huan, Shi Qing-Qing, Xue Fen, Chen Yi-Huan, Tan Qing-Rong, Wang Hua-Ning

机构信息

Department of Psychiatry, Xijing Hospital, Air Force Medical University, Xi'an 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Air Force Medical University, Xi'an 710032, China.

Department of Psychiatry, Xijing Hospital, Air Force Medical University, Xi'an 710032, China.

出版信息

J Affect Disord. 2023 Jun 15;331:217-228. doi: 10.1016/j.jad.2023.03.066. Epub 2023 Mar 24.

DOI:10.1016/j.jad.2023.03.066

PMID:36965621

Abstract

BACKGROUND

Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified.

METHODS

The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice.

RESULTS

Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS.

LIMITATIONS

The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated.

CONCLUSION

Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

摘要

背景

神经振荡在重复经颅磁刺激（rTMS）的抗抑郁作用中发挥作用。然而，高频rTMS对内侧前额叶皮质（mPFC）和海马体（HPC）神经振荡的影响及其分子机制尚未完全阐明。

方法

观察rTMS治疗后抑郁样行为、腹侧海马体（vHPC）-mPFC的局部场电位（LFP）以及HPC和mPFC中内源性大麻素系统（ECS）的变化。同时，在注射大麻素1型受体（CB1R）拮抗剂AM281或单酰甘油脂肪酶抑制剂JZL184后，也观察了抑郁样行为和LFP。此外，在谷氨酸能-CB1R和γ-氨基丁酸（GABA）能-CB1R基因敲除小鼠中进一步评估了rTMS的抗抑郁作用。

结果

rTMS减轻了内源性大麻素和能量值的变化以及mPFC-vHPC的同步性，特别是由慢性不可预测轻度应激（CUMS）诱导的θ振荡的降低。JZL184具有与rTMS相似的作用，而AM281阻断了rTMS的作用。GABA能-CB1R缺失抑制了CUMS诱导的抑郁样行为，而谷氨酸能-CB1R缺失减弱了rTMS的抗抑郁作用。