| Motion sickness (MS) is a result of the body exposed to passive movement environment, causing orientation and body balance dysfunction, with severe vestibular and autonomic reaction. There may be dizziness, headache, cold sweats, pale, nausea, vomiting syndrome that can be too serious to loss of self-care ability or operational capacity, or systemic dehydration and disturbance of electrolyte balance.The pathogenesis of motion sickness is not yet fully understood, motion sickness is considered with the integration of vestibular stimulation, visual perception stimulation and proprioception stimulation. Since 1950's, there were more than ten of theories or hypotheses on the pathogenesis of motion sickness. Most scholars accepted the "Sensory Conflict Hypothesis" or "Neural Mismatch Hypothesis".Many research findings have reported that women are more susceptible to motion sickness than men. Why is the motion sickness susceptibility gender-related? What is the pathophysiological mechanism? What is associated with the sex hormone and its receptor? There is no systematic study on these questions. According to the present subject classification, motion sickness and female hormones, especially estrogen, is two difficult issues to link.Carrying out research on this subject, can provide new understanding on etiology of motion sickness, and has important practical significance.Objective:Combinating of mouse hot-plate motion sickness model and rat "pica" motion sickness model, we explore the effects of their own estrogen level and tamoxifen on the susceptibility of motion sickness, and provide experimental basis in laboratory on "Hypothesis on susceptibility of motion sickness mediated by estrogen".Methods and Results:Part I:Effects of estrogen on susceptibility of motion sickness in the mouse rotation-hot-plate model1 Optimize the rotation-hot-plate motion sickness model in mice(1) Select the most optimal rotation stimulationWe compared motion sickness responses in mice induced by different rotation time and rotation speed, and measured the latency of paw lick in the hot plate before and after rotating for evaluating motion sickness. The results showed that 70rpm×40min or 105rpm×20min, including variable period of rotation (R) 15s+suspended (S) 5s, hot plate temperature of 55±0.5℃, mouse hot-plate response latency about 40s, too short for motion sickness was not obvious, too long, easy to burn pad of mice) was significantly longer than basic latency.(2) The relation between arginine vasopressin (AVP) and motion sickness in the mouse rotation-hot-plate motion sickness modelIn this study, we used AVP, and motion sickness score to directly confirm the feasibility of the model. The results showed that 70rpm×40min or 105rpm×20min stimulus conditions, the mice after rotating latency was significantly prolonged, and plasma AVP concentration, motion sickness score were significantly higher than control group. The results proved that the appropriate rotation stimulation can indeed induce motion sickness in mouse, so mouse hot-plate response latency as an evaluation of motion sickness can be one of the indicators.(3) Pharmacological validate the mouse rotation-hot-plate motion sickness modelFirst of all, mouse were given an effective dose of scopolamine or dealed with by chemical labyrinthectomy, and then the model-induced motion sickness, the final study results showed that mouse given scopolamine or with labyrinth damaged whose plasma AVP concentration decreased, hot plate latency as well as the motion sickness score was significantly lower than the control group. So scopolamine and chemical labyrithectomy in the model has the anti-motion sickness effects. Secondly, we combined hot-plate model with pica model in mice. Motion sickness were induced in rotation-hot-plate model, and measured by the consumption of kaolin in "pica" model. Rotation stimulated mouse showed significantly increased kaolin consumption, indicating the success of pica model, but also proving the feasibility of hot-plate model in reverse.2 Effects of estrogen on MS susceptibility in the mouse rotation-hot-plate modelWe designed several experimental approaches, aiming at the study of the effects of the levels of endogenous estrogen on mouse susceptibility of motion sickness. Mouse with surgical removal of ovaries, or given estrogen receptor antagonist tamoxifen (single dose) to artificially change the mouse endogenous estrogen levels, and by measuring plasma and pituitary AVP contents changes, and then were compared with the scopolamine and saline control group to evaluate the effects of estrogen on mouse susceptibility to motion sickness qualitatively and quantitatively.PartⅡ:the study of rats estrous cycle and estrogen levels in the "pica" model1 gender differences in rat "pica" modelSD rats were divided into four groups, the normal male and female groups, and castrated male and ovariectomized female groups. Plasma estrogen (E2) and progesterone (P) levels were determinated by ELISA, arginine vasopressin (AVP) levels were determinate by radioimmunoassay. The results showed that rotation-induced, normal female rats increased kaolin intake, meanwhile, plasma E2 and P levels were higher than normal male rats as well as plasma AVP. The ovariectomized female rats' plasma E2 and P content, as well as AVP variations lower than the normal female group, the results suggest that the motion sickness susceptibility related with gender differences and the level of estrogen in rats.2 Influences of estrous cycle and estrogen levels on rats MSWe used surgical and chemical castration ways to change endogenous estrogen levels in the estrous cycle disturbances, observed changes in estrogen levels in the case of pica in rats to explore the relation between the estrogen and motion sickness susceptibility. The results showed that the ovariectomy or estrogen receptor antagonist tamxifen may lead to lower susceptibility to motion sickness, but there was no statistically significant between the rat estrous cycle fluctuations and their motion sickness susceptibility, but there is a trend that motion sickness is serious during estrus at the highest level of estrogen.Conclusion:The mice rotation-hot-plat model using hot-plate response latency as an indicator of motion sickness is a simple, rapid and feasible experimental model of motion sickness. In combination with the model and the rat "pica" motion sickness model, we know that estrogen receptor modulators tamoxifen, endogenous estrogen secreted from ovarian have link with the susceptibility to motion sickness in rats.
|
PDF Full Text Request