Liu Chuan, Shi Ruidie, Liu Yuting, Zhao Xiangwei, Zhang Xiujun, Wang Haitao, Wu Lei, Shang Xueliang
School of Psychology and Mental Health, North China University of Science and Technology, 21 Bohai Road, Tang'shan 063210, Hebei Province, PR China; College of Basic Medical Sciences, North China University of Science and Technology, 21 Bohai Road, Tang'shan 063210, Hebei Province, PR China.
School of Psychology and Mental Health, North China University of Science and Technology, 21 Bohai Road, Tang'shan 063210, Hebei Province, PR China.
Behav Brain Res. 2023 Apr 27;444:114366. doi: 10.1016/j.bbr.2023.114366. Epub 2023 Feb 26.
Although transcranial magnetic stimulation (TMS) has been approved for the treatment of major depression, few studies have analyzed the ability of low-frequency TMS (LF-TMS) to treat depressive symptoms. Our study confirmed that LF-TMS protects the cognitive function,which can play a certain reference role in the future clinical treatment. The effectiveness of high-frequency TMS therapy has been well documented. However, the use of low-frequency TMS (LF-TMS) in the treatment of depression is rarely reported. This study aims to evaluate whether LF-TMS can reverse depression-induced cognitive impairment. We created a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm. Male C57BL/6J mice,6-8 weeks old,were randomly divided into four groups: a CON (control) group, a CUMS group, a CUMS+LF-TMS group, and a CUMS+LF-TMS+RAP (rapamycin) group. The CUMS was maintained for 28 days. LF-TMS (1 Hz) and Rap were administered for 28 days from the first day of CUMS. The mice in all groups except the control demonstrated evidence of anhedonia, anxiety, and cognitive decline on behavioral tests during the four weeks of CUMS.All the experiments were carried out under a 12-h light/dark cycle (lights on at 7 a.m.) except for the dark/light cycle reversal stimulation of CUMS. LF-TMS at 20 Mt, 1 Hz for 1 min alleviated damage to spatial cognition and synaptic plasticity in the hippocampus. Western blot analysis showed that LF-TMS reduced the down-regulation of autophagy signals in the CUMS+LF-TMS group, and enhanced the expression of synaptic plasticity-related factors, thereby improving the spatial cognitive impairment resulting from the CUMS. We concluded that LF-TMS can effectively relieve depressive behavior and cognitive dysfunction in mice subjected to CUMS by regulating autophagy signals and synaptic proteins.
尽管经颅磁刺激（TMS）已被批准用于治疗重度抑郁症，但很少有研究分析低频TMS（LF-TMS）治疗抑郁症状的能力。我们的研究证实，低频重复经颅磁刺激可保护认知功能，这对未来的临床治疗具有一定的参考作用。高频TMS治疗的有效性已有充分记录。然而，低频TMS（LF-TMS）在抑郁症治疗中的应用鲜有报道。本研究旨在评估低频重复经颅磁刺激是否能逆转抑郁引起的认知障碍。我们使用慢性不可预测轻度应激（CUMS）范式建立了抑郁症小鼠模型。将6-8周龄的雄性C57BL/6J小鼠随机分为四组：对照组、CUMS组、CUMS+LF-TMS组和CUMS+LF-TMS+雷帕霉素（RAP）组。CUMS持续28天。从CUMS第一天开始，给予LF-TMS（1Hz）和雷帕霉素28天。除对照组外，所有组的小鼠在CUMS的四周行为测试中均表现出快感缺失、焦虑和认知能力下降。除CUMS的明暗周期逆转刺激外，所有实验均在12小时光照/黑暗周期（上午7点开灯）下进行。20mT、1Hz、持续1分钟的LF-TMS减轻了海马体空间认知和突触可塑性的损伤。蛋白质免疫印迹分析表明，LF-TMS减少了CUMS+LF-TMS组自噬信号的下调，并增强了突触可塑性相关因子的表达，从而改善了CUMS导致的空间认知障碍。我们得出结论，低频重复经颅磁刺激可以通过调节自噬信号和突触蛋白有效缓解CUMS小鼠的抑郁行为和认知功能障碍。
