母代孕期应激在损伤成年子代认知功能中对CX3CL1/CX3CR1轴的影响

Effects of maternal stress during pregnancy on CX3CL1/CX3CR1 axis in impaired cognitive function of adult offspring

背景孕期应激可损害子代发育过程中中枢神经系统之间的交流,而CX3CL1/CX3CR1轴在神经元-小胶质细胞间建立了一个独特的通讯系统。目的明确孕期应激在损伤子代认知功能中是否对CX3CL1/CX3CR1轴产生影响并探究其作用机制。方法将12只SD孕鼠随机分为应激组和对照组,每组6只,应激组在孕15~21 d进行限制性应激,对照组正常饲养。用旷场、高架十字迷宫、新物体识别及Y迷宫四种行为学实验评估成年子代认知功能,ELISA检测母代及子代糖皮质激素,免疫荧光染色、Western blot检测子代海马CX3CL1、CX3CR1、Iba-1表达情况。结果母代孕期应激组及子代糖皮质激素升高(P<0.05)。母代孕期应激组子代在旷场实验中,中央区滞留时间与对照组相比减少,差异有统计学意义(P<0.05);在高架十字迷宫中进入开放臂次数和滞留时间与对照组相比减少,差异有统计学意义(P<0.05),表现出焦虑样行为;在新物体识别实验中识别指数降低(P<0.05),表现出学习记忆能力下降;在Y迷宫实验中对新异臂的识别减少(P<0.05),表现出空间记忆能力下降。母代孕期应激组子代小胶质细胞激活Iba-1表达升高,CX3CR1表达升高,CX3CL1表达下降,差异均有统计学意义(P<0.05)。结论孕期应激损害成年子代认知功能可能与CX3CL1/CX3CR1通讯障碍有关。

Background Prenatal stress may impair the connection between central nervous system during offspring development,and the CX3CL1/CX3CR1 axis establishes a unique communication system between neurons and microglia.Objective To clarify whether prenatal stress has an impact on the CX3CL1/CX3CR1 axis in impairing offspring cognitive function and explore its mechanism of action.Methods Twelve pregnant SD rats were randomly divided into prenatal stress group and control group,with 6 rats in each group.The prenatal stress group was subjected to restrictive stress on the 15th to 21st day of pregnancy,while the control group was fed normally.ELISA was used to detect plasma glucocorticoids in maternal and offspring peripheral blood,and cognitive function in adult offspring was evaluated using four behavioral methods:open field,elevated cross maze,new object recognition,and Y-maze.Immunofluorescence staining and Western blot were used to detect the expression of CX3CL1,CX3CR1,and Iba-1.Results The prenatal stress group and its offspring had elevated levels of glucocorticoids(P<0.05).In the open field experiment,the offspring of the prenatal stress group showed a significant decrease in the central area retention time compared to the control group(P<0.05),and a significant decrease in the number and retention time of entering the open arm in the elevated cross maze compared to the control group(P<0.05),indicating anxiety like behavior.In the recognition of new objects,the recognition index significantly decreased(P<0.05),indicating a decrease in learning and memory abilities.In the Ymaze,the recognition of new arms was significantly reduced(P<0.05),indicating a decrease in spatial memory abilities,and increased expression of Iba-1(P<0.05),CX3CR1(P<0.05),and CX3CL1(P<0.05)activated by prenatal stress in offspring microglia during pregnancy.Conclusion Prenatal stress damage to cognitive function in adult offspring may be related to CX3CL1/CX3CR1 communication disorders.