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Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2

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Abstract

The role of sodium channel voltage-gated beta 2 (SCN2B) in brain aging is largely unknown. The present study was therefore designed to determine the role of SCN2B in brain aging by using the senescence-accelerated mice prone 8 (SAMP8), a brain senescence-accelerated animal model, together with the SCN2B transgenic mice. The results showed that SAMP8 exhibited impaired learning and memory functions, assessed by the Morris water maze test, as early as 8 months of age. The messenger RNA (mRNA) and protein expressions of SCN2B were also upregulated in the prefrontal cortex at this age. Treatment with traditional Chinese anti-aging medicine Xueshuangtong (Panax notoginseng saponins, PNS) significantly reversed the SCN2B expressions in the prefrontal cortex, resulting in improved learning and memory. Moreover, SCN2B knockdown transgenic mice were generated and bred to determine the roles of SCN2B in brain senescence. A reduction in the SCN2B level by 60.68 % resulted in improvement in the hippocampus-dependent spatial recognition memory and long-term potential (LTP) slope of field excitatory postsynaptic potential (fEPSP), followed by an upregulation of COX5A mRNA levels and downregulation of fibroblast growth factor-2 (FGF-2) mRNA expression. Together, the present findings indicated that SCN2B could play an important role in the aging-related cognitive deterioration, which is associated with the regulations of COX5A and FGF-2. These findings could provide the potential strategy of candidate target to develop antisenescence drugs for the treatment of brain aging.

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Acknowledgments

We thank Dr. Seng Kee Leong for his valuable comments in the writing of this manuscript. This work is supported by Key Project of the Applied Basic Research Programs of Yunnan Province in China (Grant No. 2012F001), as well as the Special Fund of the Applied Basic Research Programs of Yunnan Province associated with Kunming Medical University in China (Grant No. 2013FB116).

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Authors and Affiliations

  1. Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China

    Yan-Bin XiYang, Ya Zhao, Jin Ru, Bing-Tuan Lu, Yue-Ning Zhang, Nai-Chao Wang, Jia Liu, Jin-Wei Yang, Zhao-Jun Wang, Chun-Guang Hao, Zhong-Tang Feng & Ting-Hua Wang

  2. Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China

    Yan-Bin XiYang, You-Cui Wang, Bing-Tuan Lu, Jia Liu, Zhong-Tang Feng & Ting-Hua Wang

  3. Institute of Molecular and Clinical Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China

    Wei-Yan Hu & Zhi-Cheng Xiao

  4. Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, VIC, Australia

    Wei-Yan Hu & Zhi-Cheng Xiao

  5. Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), 100021, Beijing, China

    Wei Dong, Xiong-Zhi Quan & Lian-Feng Zhang

  6. Comparative Medicine Centre, Peking Union Medical College (PUMC), 100021, Beijing, China

    Wei Dong, Xiong-Zhi Quan & Lian-Feng Zhang

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  1. Yan-Bin XiYang
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Correspondence to Lian-Feng Zhang or Ting-Hua Wang.

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Yan-Bin XiYang, You-Cui Wang, Lian-Feng Zhang, and Ting-Hua Wang contributed equally to this work.

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XiYang, YB., Wang, YC., Zhao, Y. et al. Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2. Mol Neurobiol 53, 955–967 (2016). https://doi.org/10.1007/s12035-014-9048-3

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