Wang Hua-Long, Xian Xiao-Hui, Wang Yan-Yong, Geng Yuan, Han Bing, Wang Ming-Wei, Li Wen-Bin
Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei, PR China.
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China.
Neurobiol Learn Mem. 2015 Feb;118:1-7. doi: 10.1016/j.nlm.2014.11.002. Epub 2014 Nov 8.
Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to increase the excitability of neurons, and it induces long-term effects that can improve symptoms related to neurodegenerative diseases, including cognitive ability. The present study was undertaken to identify the mechanism by which rTMS improves cognitive impairments in mice. The novel object recognition test in vivo was used to evaluate the cognitive function of the mice. Whole-cell patch-clamp recordings were used to evaluate the neuronal excitability, including the resting membrane potential, the number of action potentials induced by depolarized current, after-hyperpolarization, and the voltage-dependent Ca(2+) current in hippocampal slices. We found that the aged mice showed impairments in cognitive function, and high-frequency (25Hz) rTMS for 14 consecutive-days ameliorated the impairments. Whole-cell patch-clamp recordings showed that, compared to matured mice, the hippocampal CA1 pyramidal neurons of aged mice showed significantly hyperpolarized resting membrane potential, significantly decreased numbers of action potentials after injection of depolarizing current, and significantly increased after-hyperpolarization after an action potential. The exposure to high-frequency rTMS significantly improved the above deficits in the neuronal excitability in the aged rTMS mice. Consistent with the above changes, the exposure to high-frequency rTMS also significantly decreased the voltage-dependent Ca(2+) current of the neurons compared with the aged sham mice. These data suggested that the rTMS could improve the age-related cognitive impairment in parallel with regulating the neuronal excitability and modifying the voltage-dependent Ca(2+) channels.
慢性高频重复经颅磁刺激(rTMS)是一种增加神经元兴奋性的非侵入性方法,它能诱导产生长期效应,改善与神经退行性疾病相关的症状,包括认知能力。本研究旨在确定rTMS改善小鼠认知障碍的机制。采用体内新颖物体识别试验评估小鼠的认知功能。使用全细胞膜片钳记录来评估神经元兴奋性,包括静息膜电位、去极化电流诱导的动作电位数量、超极化后电位以及海马切片中的电压依赖性Ca(2+)电流。我们发现老年小鼠存在认知功能障碍,连续14天的高频(25Hz)rTMS改善了这些障碍。全细胞膜片钳记录显示,与成年小鼠相比,老年小鼠海马CA1锥体神经元的静息膜电位显著超极化,注入去极化电流后动作电位数量显著减少,动作电位后的超极化后电位显著增加。高频rTMS处理显著改善了老年rTMS小鼠神经元兴奋性的上述缺陷。与上述变化一致,与老年假手术小鼠相比,高频rTMS处理还显著降低了神经元的电压依赖性Ca(2+)电流。这些数据表明,rTMS可以通过调节神经元兴奋性和改变电压依赖性Ca(2+)通道来改善与年龄相关的认知障碍。
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