中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 916-924.doi: 10.4103/1673-5374.158356

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

低频经颅磁刺激增强老年大脑海马突触可塑性

  

  • 收稿日期:2015-04-20 出版日期:2015-06-18 发布日期:2015-06-18
  • 基金资助:

    河北省自然科学基金(H2015206409)；河北省高等学校科学技术研究项目(QN20131068, QN2014140)；河北省卫生计生委2014年度医学科学研究重点课题(ZL20140017)；河北省科技项目(132777209, 132777135)

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

Zhan-chi Zhang 1, Feng Luan 2, Chun-yan Xie 3, Dan-dan Geng 1, Yan-yong Wang 4, 5, Jun Ma 1, 5   

  1. 1 Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei Province, China
    2 Department of Otorhinolaryngology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    3 Second Surgical Department, Qinghe Public Hospital of Hebei Province, Xingtai, Hebei Province, China
    4 Department of Neurology, First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
    5 Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Shijiazhuang, Hebei Province, China
  • Received:2015-04-20 Online:2015-06-18 Published:2015-06-18
  • Contact: Ma Jun, M.D., 13933113125@163.com
  • Supported by:

    This work was supported by the Natural Science Foundation of Hebei Province of China, No. H2015206409; Science and Technology Research Youth Fund Project of Hebei Colleges and Universities in China, No. QN20131068, QN2014140; a grant from Health and Family Planning Commission Medical Scientific Research Project in Hebei Province of China, No. ZL20140017 and a grant from Hebei Science and Technology Support Program Project of China, No. 132777209, 132777135.

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摘要：

研究已证实低频经颅磁刺激可增强突触可塑性，改善认知功能缺损小鼠空间认知功能，但其对正常衰老致认知功能和大脑突触可塑性降低的影响尚未可知。为此，实验旨在揭示低频经颅磁刺激对正常衰老小鼠海马脑源性神经营养因子信号通路，及其下游调节因子Src酪氨酸激酶Fyn、下降效应因子突触素和生长相关蛋白43的影响，从而明确前述影响的产生机制。结果显示，低频经颅磁刺激（刺激强度11%静息运动阈值，1Hz）激活老年小鼠海马脑源性神经营养因子及其受体TrkB和Fyn，上调突触蛋白标志突触素和生长相关蛋白43mRNA和蛋白表达。由此，我们认为脑源性神经营养因子信号通路在维持和调节低频经颅磁刺激诱导的老年小鼠大脑海马结构性突触可塑性、改善认知功能方面有重要作用。

关键词: 神经再生, 非侵袭性大脑刺激, 经颅磁刺激, 神经营养因子, 脑源性神经营养因子, 神经可塑性, 海马, 老年, 认知功能

Abstract:

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Key words: neural regeneration, non-invasive brain stimulation, transcranial magnetic stimulation, neurotrophic factor, brain-derived neurotrophic factor, neuroplasticity, hippocampus, aging, cognitive function