title: Sodium Channel Voltage-Gated Beta 2 Plays a Vital Role in Brain Aging Associated with Synaptic Plasticity and Expression of COX5A and FGF-2.
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.
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: XiYang
authors.affiliation: Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: You-Cui
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ru
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Bing-Tuan
authors.initials: BT
authors.lastname: Lu
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Yue-Ning
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Nai-Chao
authors.initials: NC
authors.lastname: Wang
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, VIC, Australia.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
authors.forename: Chun-Guang
authors.initials: CG
authors.lastname: Hao
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zhong-Tang
authors.initials: ZT
authors.lastname: Feng
authors.affiliation: Institute of Molecular and Clinical Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.|Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, VIC, Australia.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), 100021, Beijing, China.|Comparative Medicine Centre, Peking Union Medical College (PUMC), 100021, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), 100021, Beijing, China.|Comparative Medicine Centre, Peking Union Medical College (PUMC), 100021, Beijing, China.
authors.forename: Xiong-Zhi
authors.initials: XZ
authors.lastname: Quan
authors.affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS), 100021, Beijing, China. lianfeng_zhang3@yahoo.com.cn.|Comparative Medicine Centre, Peking Union Medical College (PUMC), 100021, Beijing, China. lianfeng_zhang3@yahoo.com.cn.
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China. tinghua_neuron@263.net.|Institute of Neurological Disease, State Key Lab of Biotherapy, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China. tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D018782:Maze Learning; D008568:Memory; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D062548:Voltage-Gated Sodium Channel beta-2 Subunit / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C540272:SCN2B protein, mouse; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D016222:Fibroblast Growth Factor 2; C547699:Cox5a protein, mouse; D003576:Electron Transport Complex IV
keywords: Aging; Gastrodiae; SAMP8; SCN2B; Synaptic plasticity; Xueshuangtong