Department of Military Hygiene, Faculty of Naval Medicine, Second Military Medical University, 800 Xiang Yin Road, Shanghai, China.
Brain Res. 2012 Jun 21;1461:30-40. doi: 10.1016/j.brainres.2012.04.041. Epub 2012 Apr 28.
Repeated exposure to a provocative motion stimulus leads to motion sickness habituation indicative of the existence of central processes to counteract the disturbing properties of the imposed motion. In the present study, we attempt to investigate whether NMDA and GABA(A) receptors in rat caudal vestibular nucleus neurons are involved in motion sickness habituation induced by repeated Ferris-wheel like rotation in daily session (2h/d). We showed that defecation response increased and spontaneous locomotion decreased within 4 sessions (sickness phase). They recovered back to the control level after 7 sessions (habituation phase). Western blot analysis found that NMDA receptor signal molecules: calmodulin protein kinase II and cAMP response element-binding protein (CREB) were both activated during sickness phase, while a prolonged CREB activation was also observed during habituation phase. Real-time quantitative PCR revealed an increase in c-fos and a decrease in Arc mRNA level during sickness phase. We also found an increase in GABA(A) receptor α1 subunit (GABA(A) α1) protein level in this stage. These results suggested that altered NMDA receptor signaling and GABA(A) receptor expression level in caudal vestibular nucleus were associated with motion sickness habituation. Furthermore, immunofluorescence and confocal laser scanning microscopy showed that the number of GABA(A) α1 immunolabeled neurons in caudal vestibular nucleus increased while the number of GABA(A) α1/Arc double labeled neurons and the average amount of Arc particle in soma of these neurons decreased during sickness phase. It suggested that GABA(A) receptor level might be negatively regulated by Arc protein in caudal vestibular nucleus neurons.
反复暴露于刺激性运动刺激会导致运动病习惯化，这表明存在中枢过程来抵消强制运动的干扰特性。在本研究中，我们试图研究 NMDA 和 GABA(A) 受体在大鼠前庭神经核神经元中是否参与了由每日 Ferris 轮样旋转（2h/d）引起的运动病习惯化。我们发现，在 4 个疗程（疾病期）内，排便反应增加，自发运动减少。在 7 个疗程后（习惯化期），它们恢复到对照水平。Western blot 分析发现，NMDA 受体信号分子：钙调蛋白激酶 II 和 cAMP 反应元件结合蛋白（CREB）在疾病期均被激活，而在习惯化期也观察到 CREB 的延长激活。实时定量 PCR 显示，在疾病期 c-fos 和 Arc mRNA 水平增加，Arc mRNA 水平降低。我们还发现该阶段 GABA(A) 受体 α1 亚基（GABA(A)α1）蛋白水平增加。这些结果表明，前庭神经核中 NMDA 受体信号和 GABA(A) 受体表达水平的改变与运动病习惯化有关。此外，免疫荧光和共聚焦激光扫描显微镜显示，在疾病期，前庭神经核中 GABA(A)α1 免疫标记神经元的数量增加，而 GABA(A)α1/Arc 双标记神经元的数量和这些神经元体中 Arc 颗粒的平均数量减少。这表明 GABA(A) 受体水平可能在前庭神经核神经元中被 Arc 蛋白负调控。
