| ObjectivesThis study used a rat model of modified multiple platform method(MMPM) as the research object, from a praxiology point of view to explore the antimanic effects of acupuncture, taking the balance regulation system of Glu / GABA as the pointcut, to detect the expression of GABA and GLU neurons in the hippocampal of rats, and the expression level of protein of Glutamate NMDA receptor subunit and GABAA receptor in order to study the molecular mechanisms of pathological changes of excitement and inhibition of Glu/GABA in the manic state. Besides, we aimed to discuss the central mechanism and molecular targets of antimanic effects of acupuncture and to provide a scientific basis and foundation for the application of anxiety treatment. Methods60 SD rats, 30 rats were male and 30 rats were female, were divided randomly into five groups(the blank control group, model group, sodium valproate group, point acupuncture group and non-point acupuncture group), with 12 rats in each group. The modified multiple platform method(MMPM) was used to establish mania rats model. We do acupuncture therapy to the rats in the acupuncture group and non-point group. The acupuncture last 30 minutes each time, once per day. The acupuncture group were acupunctured the "Baihui", "Neiguan" and "Sanyinjiao" points of rats. The non-point group were acupunctured beside the above 3 points of acupuncture points. The rats in the valproate group were given suspension of valproate by intragastric administration(300mg/kg), once per day. All corresponding intervention was continued for seven days.After the experiment, we observed the spirit, behavior, recorded the first time that the rats fell asleep after they left from the water environment(that is sleep latency), and open field test. The eighth day, the all rats were killed, then we detected the expression of GABA and GLU neurons in the hippocampal of rats, and the protein expression of Glutamate NMDA receptor subunits NR1, NR2 A, NR2 B and GABAA receptor of in the hippocampal of all rats. Results: 1. The change of spirit and behaviorThe second day after sleep deprivation, the rats of modle group were excited and ran about between different platforms. They were sensitive to slight sound and light stimulation, and were fear of sound and light. Three days after sleep deprivation, the rats of modle group were dull. The muscles of head and face twitched slightly with whiskers moving. They felt sleepy when they squatted down on the platforms.The rats often fell in the water again and again for a nap and climbed up the platform after waking up. Their activities and food intake got less. Aggressive behavior such as biting appeared after stimulation. 5 ~ 7 days after sleep deprivation, the rats of modle group were depressed, and their activities and food intake got less. The whole body hair of rats rose. The rats became irritability extremely, and their behavior of bite attack increased. In addition to the blank control group, the behavior of the rest of group is similar. 2. Sleep latencyThe sleep latency of the model group was significantly longer than the blank control group, and the difference was statistically significant(P<0.01), which suggested that model establishment can lead to extended sleep latency of rats. And the sleep latency of every rat in the group was more than 30 min, which proved successful model. Compared with the model group, the sleep latency of the three therapeutic group was obviously shorter, the difference was statistically significant(P<0.01). Three treatment group were compared in pairs, the sleep latency of the point acupuncture group and the sodium valproate group was significantly shorter than that of non-point acupuncture group(P<0.01; P<0.05).But there was no significant difference between the point acupuncture group and the sodium valproate group(P>0.05). That indicated that sodium sodium valproate, point acupuncture and non-point acupuncture can prevent mania from extending sleep latency.It also revealed that the therapeutic effect of point acupuncture and sodium valproate was equal and is superior to the effect of non-point acupuncture. 3. Open field testCompared with the blank control group, the horizontal movements scores of model group were obviously lower(P<0.01), which suggested that model establishment can reduce the horizontal movements of rats. Compared with the model group, the horizontal movements scores of the sodium valproate group and the non-point acupuncture group were no statistically significant(P>0.05), and the horizontal movements scores of the point acupuncture group were higher than the model group(P <0.05).But there was no significant difference between the point acupuncture group and the blank control group(P>0.05). The horizontal movements scores of the sodium valproate group and the non-point acupuncture group were obviously lower than the point acupuncture group(P<0.05). Compared with the blank control group, the vertical movements scores of model group were obviously lower(P<0.05), which suggested that model establishment can reduce the vertical movements of rats. Compared with the model group, the vertical movements scores of the sodium valproate group, the point acupuncture group and the non-point acupuncture group were no statistically significant(P>0.05), which suggested that the three intervening measures had no obvious effect on vertical movements of rats. 4 The expression of GLU and GABA neuronsCompared with the blank control group, the expression of Glu neurons in hippocampal CA1 and CA3 regions of model group rats was significantly increased(P<0.01), and the expression of GABA neurons was significantly reduced(P < 0.01), which suggested that sleep deprivation could cause the increase of Glu content and the decrease of GABA content in hippocampal of rats. Compared with the model group, the expression of Glu neurons in hippocampal of the sodium valproate group and point acupuncture group decreased significantly(P<0.01), and the expression of GABA neurons increased significantly(P<0.01, P<0.05), but there was no significant difference between the sodium valproate group and the point acupuncture group(P>0.05). The results indicated that sodium valproate and point acupuncture could cause the increase of Glu content and the decrease of GABA content in hippocampal of rats, and that non-point had no such effect. 5 Protein expression of hippocampal NMDA receptor subunits NR1, NR2 A and NR2 B and GABAARCompared with the blank group, the expression of NR2 B in model group increased significantly(P<0.01). Compared with the model group, the expression of NR2 B in the sodium valproate group and the point acupuncture group decreased significantly(P<0.05), but it had no significant difference in non-point acupuncture group(P>0.05). The sodium valproate group and the point acupuncture group had no significant difference(P>0.05). The expression of NR1, NR2 A and GABAAR had no significant difference among the 5 groups(P > 0.05). Conclusions 1. Point acupuncture can correct the extension of the sleep latency of manic model.It also can alleviate partial behavioral inhibition in the condition of energy consumption due to the long-term sleep deprivation, and the effect is much better than sodium valproate and non-point acupuncture. 2. Model establishment by sleep deprivation can cause the increase of Glu content and the decrease of GABA content in hippocampal CA1 and CA3 regions of rats. Sodium valproate and point acupuncture can effectively improve the imbalance of Glu and GABA content in hippocampal CA1 and CA3 regions of rats because of sleep deprivation, but non-point acupuncture cannot play this role. This showes that adjusting the imbalance of Glu and GABA content in hippocampus may be one of the neurobiological mechanisms how sodium valproate and point acupuncture resist to mania. 3. Sleep deprivation can make the expression of Glu NMDA receptor NR2 B increase, the way that sodium valproate and acupuncture resist to mania may be related to the reduction of NR2B’s expression and the reduction of Glu’s excitotoxicity. |
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