title: Low level of swiprosin-1/EFhd2 in vestibular nuclei of spontaneously hypersensitive motion sickness mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ling-Chang
authors.initials: LC
authors.lastname: Tong
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Basal medical College, Dalian Medical University, Dalian, Liaoning 130041, China.
authors.forename: Wei-Heng
authors.initials: WH
authors.lastname: Su
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei-Ye
authors.initials: WY
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: Basal medical College, Dalian Medical University, Dalian, Liaoning 130041, China.
authors.forename: Tong-Hui
authors.initials: TH
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.affiliation: Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry; D018345:Mice, Knockout; D009041:Motion Sickness / Q000473:pathology*; D040901:Proteomics; D014726:Vestibular Nuclei / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; C530752:EFHD2 protein, mouse