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

摘要

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 re-ceptor (FXR),a nuclear hormone receptor,acts on neurological behaviors such as emotion,social behav-ior,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 in-teraction test (SIT ), and passive avoidance test (PAT),and the contents of neurotransmitters were de-termined by the LC-MS /MS method in FXR knockout (KO)female mice and their wild-type controls.Re-sults FXR KO mice showed significantly increased immobility time in FST (P <0.01 ),and it showed in-creased 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.Mo-reover,in SIT,FXR KO mice had remarkably in-creased 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 pre-frontal cortex,none of the neurotransmitters examined showed any difference between FXR KO mice and their controls.Conclusion FXR may be involved in main-tenance of the homeostasis of neural transmission in the central nervous system,thereby influences the emotion-al and social behavior in animals.