肝X受体激动剂对抑郁模型小鼠海马树突棘数目的影响

The effects of LXRs agonist on the number of hippocampal dendritic spines in a mouse model of depression

目的:探讨肝X受体(LXRs)激动剂GW3965对慢性不可预知性应激(CUS)诱导的抑郁症模型小鼠海马结构各亚区CA1、CA3和DG内树突棘数目变化的影响。方法:选取雄性C57BL/6J小鼠,经过适应性喂养和糖水基线调整后,被随机分为对照组(control)、对照+GW3965组(GW)、抑郁模型组(CUS)以及抑郁模型+GW3965组(CUS/GW)。CUS组和CUS/GW组小鼠接受连续10周的CUS干预,GW组和CUS/GW组小鼠在CUS干预的第7周开始接受4周的GW3965给药。第10周末进行行为学测试,之后应用免疫组化及现代体视学技术精准定量小鼠海马结构各亚区树突棘密度和总数目改变。结果:持续数周的应激使小鼠的体质量及糖水偏好百分比明显下降,强迫游泳不动时间显著增加。体视学结果显示CUS干预使小鼠CA1、CA3和DG区树突棘密度和数量明显减少。4周GW3965治疗改善了小鼠的抑郁样行为及逆转了DG区树突棘密度和总数目的下降。结论:LXRs激动剂GW3965对CUS模型小鼠DG区树突棘总数目的影响可能是其发挥抗抑郁作用的神经生物学基础之一。

Objective:To investigate the effect of liver X receptor(LXRs)agonist GW3965 on the number of dendritic spines in each subarea of hippocampus(CA1,CA3 and DG)in depression mice induced by chronic unpredictable stress(CUS).Methods:Male C57BL/6J mice were randomly divided into control group,control+GW group(GW),CUS group and CUS+GW group(CUS/GW)after adaptive feeding and adjustment of base line.Mice in the CUS and CUS/CW groups were subjected to CUS intervention for 10 consecutive weeks.The mice in the GW and CUS/CW groups were injected with CW3965 for 4 weeks from the 7th week of CUS intervention.Behavioral tests were performed at the end of the 1th week.Immunohistochemistry and modern stereology techniques were used to precisely quantify the changes in the density and numbers of dendritic spines in hippocampal subregions.Results:Stress lasting for several weeks significantly decreased the body weight and the sucrose preference of mice,and significantly increased the immobility time of forced swimming test.Stereological results showed that CUS significantly reduced the density and number of dendritic spines in hippocampus subregions(CAl,CA3 and DG)of mice.Four weeks of CW3965 treatment improved the depression-like behavior and reversed the decline of the dendritic spine density and total number in the DG of mice.Conclusion:The effects of LXRs agonist GW3965 on the total numbers of dendritic spine in CUS model mice may be one of the neurobiological bases of its antidepressant effect.