Neural Regeneration Research ›› 2015, Vol. 10 ›› Issue (6): 916-924.doi: 10.4103/1673-5374.158356

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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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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