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.
Highlights
In a previous study conducted in our laboratory, we noticed significant variations in the susceptibility to Motion sickness (MS) in mice, and the MS index was normally distributed[22]
To unravel the genetic basis of the varying susceptibility to MS, we obtained sensitive to MS (SMS) and resistant to MS (RMS) strains by phenotype-guided breeding using genetically heterogeneous outbred mice as the founders (Fig. 1a,b)
Swiprosin-1 was differentially expressed in the brains of two mouse strains with varying MS sensitivities (SMS and RMS)
Summary
Scopolamine and dimenhydrinate are the main anti-MS drugs currently available. Both agents are highly sedative due to general depression of the central nervous system. Twin studies demonstrated familial aggregation and significant heritability[19,20]. These findings highlight the importance of genetic factors in determining susceptibility to MS. The goal of the current study was to establish a genetic animal model that is hypersensitive to MS and to explore the possible factors governing MS susceptibility. Proteomics studies revealed decreased expression of swiprosin-1, a protein selectively expressed in VN neurons, in SMS mice. We found that swiprosin-1 is an anti-MS protein
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
