法尼醇X受体基因缺失对雌性小鼠神经行为及神经传递系统的影响

Effects of FXR gene deletion on neurobehaviors and neurotransmission systems in female mice

目的探讨法尼醇X受体(farnesoid X receptor,FXR)作为一种核激素受体对情感、社交或记忆等神经行为的调节作用。方法通过一系列行为学测试,包括高架十字迷宫,强迫游泳、社交活动和避暗,以及LC-MS/MS法检测大脑不同区域的神经递质,评估FXR基因敲除(knockout,KO)对♀小鼠中枢神经系统功能的影响。结果 FXR KO导致小鼠在强迫游泳中不动时间延长(P<0.01),进入高架十字迷宫开放臂次数增加(P<0.01),逗留时间延长,同时社交活动增强(P<0.01),但对避暗行为中的潜伏期和错误次数无明显影响。FXR KO亦导致小鼠海马γ-氨基丁酸(GABA,P<0.05)、谷氨酸(Glu,P<0.05)、去甲肾上腺素(NE,P<0.01)以及GABA/Glu(P<0.05)明显降低,但对前额叶相关神经递质无明显影响。结论 FXR可能参与调控中枢神经系统中神经递质稳态平衡,进而影响动物的情感和社交行为。

Aim To investigate how Farnesoid X receptor（ FXR）,a nuclear hormone receptor,acts on neurological behaviors such as emotion,social behavior,memory and so on. Methods FXR＇s function in central nervous system was evaluated by conducting a battery of behavioral tests including elevated plus maze test（ EPMT）,forced-swimming test（ FST）,social interaction test（ SIT）, and passive avoidance test（ PAT）,and the contents of neurotransmitters were determined by the LC-MS / MS method in FXR knockout（ KO） female mice and their wild-type controls. Results FXR KO mice showed significantly increased immobility time in FST（ P〈 0. 01）,and it showed increased tendency to enter the open arms in EMPT（ P〈 0. 01）. The number of probing the open arms by FXR KO mice was more than that of the controls. Moreover,in SIT,FXR KO mice had remarkably increased sniffing interactions with the stranger mouse in the same cage（ P〈 0. 01）. But in PAT,the latency for FXR KO mice to enter the dark chamber on the test day and the number of FXR KO mice to enter the dark chamber didn ＇t differ from those wild-type mice. In hippocampus,the contents of GABA,Glu,and NE were decreased prominently in FXR KO mice（ P〈 0. 05,P〈 0. 05 and P〈 0. 01,respectively） as well as the ratio of GABA to Glu（ P〈 0. 05）. But in prefrontal cortex,none of the neurotransmitters examined showed any difference between FXR KO mice and their controls. Conclusion FXR may be involved in maintenance of the homeostasis of neural transmission in the central nervous system,thereby influences the emotional and social behavior in animals.