Abstract
ObjectiveTo identify differentially expressed genes associated with motion sickness (MS) susceptibility in the rat caudal vestibular nucleus.MethodsWe identified MS susceptible (MSS) and insusceptible (inMSS) rats by quantifying rotation-induced MS symptoms: defecation and spontaneous locomotion activity. Microarray analysis was used to screen differentially expressed genes in the caudal vestibular nucleus (CVN) after rotation. Plasma stress hormones were identified by radioimmunoassay. Candidate genes were selected by bioinformatics analysis and the microarray results were verified by real-time quantitative-PCR (RT-qPCR) methods. By using Elvax implantation, receptor antagonists or recombinant adenovirus targeting the candidate genes were applied to the CVN to evaluate their contribution to MS susceptibility variability. Validity of gene expression manipulation was verified by RT-qPCR and western blot analysis.ResultsA total of 304 transcripts were differentially expressed in the MSS group compared with the inMSS group. RT-qPCR analysis verified the expression pattern of candidate genes, including nicotinic cholinergic receptor (nAchR) α3 subunit, 5-hydroxytryptamine receptor 4 (5-HT4R), tachykinin neurokinin-1 (NK1R), γ-aminobutyric acid A receptor (GABAAR) α6 subunit, olfactory receptor 81 (Olr81) and homology 2 domain-containing transforming protein 1 (Shc1). In MSS animals, the nAchR antagonist mecamylamine significantly alleviated rotation-induced MS symptoms and the plasma β-endorphin response. The NK1R antagonist CP99994 and Olr81 knock-down were effective for the defecation response, while the 5-HT4R antagonist RS39604 and Shc1 over-expression showed no therapeutic effect. In inMSS animals, rotation-induced changes in spontaneous locomotion activity and the plasma β-endorphin level occurred in the presence of the GABAAR antagonist gabazine.ConclusionOur findings suggested that the variability of the CVN gene expression profile after motion stimulation might be a putative molecular basis for individual differences in MS susceptibility and provide information for the development of new therapeutic strategies for MSS individuals.
Highlights
Motion sickness (MS) is a syndrome of autonomic reactions, such as nausea, vomiting, pallor, sweating, increased salivation and stomach awareness, which are commonly provoked by externally imposed motion [1,2]
The differential gene expression profile that we identified might be exclusively related to the difference in functional alteration in caudal vestibular nucleus (CVN) neurons between animals differing in MS susceptibility properties, but not to common responses induced by vestibular stimulation
There are apparent individual differences with respect to MS susceptibility in rats and that MS susceptible (MSS) and inMSS animals can be separated from the normal adult male population by assessing rotation-induced defecation and spontaneous locomotion in combination
Summary
Motion sickness (MS) is a syndrome of autonomic reactions, such as nausea, vomiting, pallor, sweating, increased salivation and stomach awareness, which are commonly provoked by externally imposed motion [1,2]. According to the ‘postural instability theory’, the occurrence of motion sickness may be associated with preceding unstable postural control at locomotive surroundings on mobile devices [5,6,7]. These theories do not explain apparent individual differences in MS susceptibility, let alone provide detailed information on the underlying molecular bases and mechanisms [8]. A recent study confirmed that neurons in the CVN constitute principal parts of neural networks that contribute to autonomic manifestations, such as retching, excessive salivation, defecation and urination during galvanic vestibular stimulation in felines [23]. Based on the idea that neurons in the CVN participate in triggering motion sickness, it is conceivable that they might contribute to the variability in MS susceptibility
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