Low level of swiprosin-1/EFhd2 in vestibular nuclei of spontaneously hypersensitive motion sickness mice

Wang, ZB; Han, P; Tong, LC; Luo, Y; Su, WH; Wei, X; Yu, XH; Liu, WY; Zhang, XH; Lei, H; Li, ZZ; Wang, F; Chen, JG; Ma, TH; Su, DF; Li, L

Li, L (reprint author), Second Mil Med Univ, Dept Pharmacol, Coll Pharm, Shanghai 200433, Peoples R China.; Chen, JG (reprint author), Huazhong Univ Sci & Technol, Dept Pharmacol, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China.; Ma, TH (reprint aut

Scientific Reports, 2017; 7 ( ):


Susceptibility to motion sickness (MS) varies considerably among humans. However, the cause of such variation is unclear. Here, we used a classical genetic approach to obtain mouse strains highly sensitive and resistant to MS (SMS and RMS). Proteomics analysis revealed substantially lower swiprosin-1 expression in SMS mouse brains. Inducing MS via rotary stimulation decreased swiprosin-1 in the mouse brains. Swiprosin-1 knockout mice were much more sensitive to motion disturbance. Immunohistochemistry revealed strong swiprosin-1 expression in the vestibular nuclei (VN). Over-expressing swiprosin-1 in the VN of SMS mice decreased MS susceptibility. Down-regulating swiprosin-1 in the VN of RMS mice by RNAi increased MS susceptibility. Additional in vivo experiments revealed decreased swiprosin-1 expression by glutamate via the NMDA receptor. Glutamate increased neuronal excitability in SMS or swiprosin-1 knockout mice more prominently than in RMS or wild-type mice. These results indicate that swiprosin-1 in the VN is a critical determinant of the susceptibility to MS.

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