机构：[1]Institute of Neuroscience, Basic Medical College, Kunming Medical University, Kunming, Yunnan, PR China[2]Department of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, PR China[3]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China[4]Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China[5]School of Stomatology, Kunming Medical University, Kunming, Yunnan, PR China[6]Experiment Center for Medical Science Research, Kunming Medical University, Kunming, Yunnan, PR China[7]Physical Education Department, Kunming Medical University, Kunming, Yunnan, PR China[8]Department of Neurology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, PR China内科片神经内科云南省第一人民医院[9]Basic Medical College, Kunming Medical University, Kunming, Yunnan, PR China[10]Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, PR China[11]Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Clayton, VIC, Australia[12]Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences(CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing, China
Voltage-gated sodium channels beta 2 (Nav beta 2, encoded by SCN2B) is a substrate of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and regulates cell surface expression of channels in neurons. Previous studies reported enhanced Nav beta 2 processing by BACE1 in Alzheimer's disease (AD) model and patients. We investigated whether changes in Nav beta 2 expression affect neuronal seizure and amyloid precursor protein (APP) processing in an AD mouse model. Our study used eight-month-old APP/presenilin 1 (PS1) mice and transgenic Nav beta 2 knockdown [by 61% vs. wild type (WT)] APP/PS1 mice (APP/PS1/Nav beta 2-kd), with age-matched WT and Nav beta 2 knockdown (Nav beta 2-kd) mice as controls. We found that Nav beta 2 knockdown in APP/PS1 mice partially reversed the abnormal Nav beta 2 cleavage and the changes in intracellular and total Nav1.1 alpha expression. It also restored sodium currents density in hippocampal neurons and neuronal activity, as indicated by EEG tracing; improved Morris water maze performance; and shifted APP amyloidogenic metabolism towards non-amyloidogenic processing. There were no differences in these indicators between WT and Nav beta 2-kd mice. These results suggest Nav beta 2 knockdown may be a promising strategy for treating AD.
基金：
National Natural Science Foundation of China (Grant Nos. 81560238 and 81502377), the Fund of the Applied Basic Research Programs of Yunnan Province in China (Grant Nos. 2016FB139 and 2016FB123), and the Special Fund of the Applied Basic Research Programs of Yunnan Province associated with Kunming Medical University in China (Grant Nos. 2015FB001 and 2014FB087).
第一作者机构：[1]Institute of Neuroscience, Basic Medical College, Kunming Medical University, Kunming, Yunnan, PR China[2]Department of Laboratory Medicine, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, PR China
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推荐引用方式(GB/T 7714)：
Hu Tao,Xiao Zhangang,Mao Rui,et al.Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing[J].ONCOTARGET.2017,8(59):99284-99295.doi:10.18632/oncotarget.21849.
APA：
Hu, Tao,Xiao, Zhangang,Mao, Rui,Chen, Bo,Lu, Min-Nan...&Xiyang, Yan-Bin.(2017).Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing.ONCOTARGET,8,(59)
MLA：
Hu, Tao,et al."Nav beta 2 knockdown improves cognition in APP/PS1 mice by partially inhibiting seizures and APP amyloid processing".ONCOTARGET 8..59(2017):99284-99295
