Differential Gene Expression Profile in the Rat Caudal Vestibular Nucleus is Associated with Individual Differences in Motion Sickness Susceptibility.
Differential Gene Expression Profile in the Rat Caudal Vestibular Nucleus is Associated with Individual Differences in Motion Sickness Susceptibility.
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大鼠前庭尾核的差异基因表达谱与晕动病易感性的个体差异相关
DOI：
10.1371/journal.pone.0124203
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Cai YL
中科院分区：
文献类型：
--
作者：
Wang JQ;Qi RR;Zhou W;Tang YF;Pan LL;Cai YL
目的 鉴定大鼠前庭尾核中与晕动病（MS）易感性相关的差异表达基因。方法 我们通过量化旋转引起的多发性硬化症症状（排便和自发运动活动）来鉴定多发性硬化症易感（MSS）和不敏感（inMSS）大鼠。采用微阵列分析筛选旋转后尾部前庭核（CVN）中差异表达的基因。通过放射免疫测定法鉴定血浆应激激素。通过生物信息学分析选择候选基因，并通过实时定量PCR（RT-qPCR）方法验证微阵列结果。通过使用 Elvax 植入，将针对候选基因的受体拮抗剂或重组腺病毒应用于 CVN，以评估它们对 MS 易感性变异的贡献。通过 RT-qPCR 和蛋白质印迹分析验证了基因表达操作的有效性。结果MSS组与inMSS组相比共有304个转录本存在差异表达。 RT-qPCR分析验证了候选基因的表达模式，包括烟碱胆碱能受体（nAchR）α3亚基、5-羟色胺受体4（5-HT4R）、速激肽神经激肽-1（NK1R）、γ-氨基丁酸A受体（GABAAR）α6亚基、嗅觉受体81（Olr81）和含同源2结构域的转化蛋白1（Shc1）。在 MSS 动物中，nAchR 拮抗剂美加明显着减轻了旋转引起的 MS 症状和血浆 β-内啡肽反应。 NK1R拮抗剂CP99994和Olr81敲低对排便反应有效，而5-HT4R拮抗剂RS39604和Shc1过表达则没有治疗作用。在 inMSS 动物中，在 GABAAR 拮抗剂加巴嗪存在的情况下，旋转引起的自发运动活动和血浆 β-内啡肽水平发生变化。结论 我们的研究结果表明，运动刺激后 CVN 基因表达谱的变异性可能是 MS 易感性个体差异的假定分子基础，并为 MSS 个体开发新的治疗策略提供信息。
Objective To identify differentially expressed genes associated with motion sickness (MS) susceptibility in the rat caudal vestibular nucleus. Methods We 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. Results A 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. Conclusion Our 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.
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