NRG1及其受体ErbB4在大鼠不同发育阶段不同脑区表达及与抑郁认知功能关系研究

Expression of NRG1 and its receptor ErbB4 in different brain regions at different developmental stages and its relationship with cognitive function in depressed rats

目的:研究不同发育阶段不同脑区神经调节蛋白1(NRG1)及其受体ErbB4的表达及其与抑郁大鼠认知功能的关系。方法:取新生鼠(出生后15 d)、幼年鼠(出生后30 d)和成年鼠(出生后90 d)各20只,组内随机分为对照组和模型组各10只,采用慢性不可预见性轻度应激方法(CUMS)建立大鼠抑郁模型。观察大鼠一般情况,采用旷场实验(OFT)进行大鼠自主活动测试,采用Morris水迷宫定向航行测试和空间探索测试评价大鼠的学习和记忆功能,通过RT-PCR法检测大鼠海马及前额皮层组织NRG1、ErbB4基因水平的表达。结果:与同龄对照组相比,新生、幼年以及成年模型组大鼠在建模10 d及21 d时体重明显下降(P<0.05)。与同龄对照组相比,新生模型组与幼年模型组大鼠水平运动和垂直运动得分均显著降低(均P<0.05)。与新生模型组相比,幼年及成年模型组大鼠水平运动和垂直运动得分均显著增加,成年模型组高于幼年模型组(均P<0.05)。与同龄对照组相比,新生模型组和幼年模型组大鼠逃避潜伏期和游泳距离显著增加,穿越平台次数显著降低(均P<0.05)。与新生模型组相比,幼年及成年模型组大鼠逃避潜伏期和游泳距离显著降低,幼年模型组高于成年模型组,穿越平台次数显著增加,幼年模型组低于成年模型组(均P<0.05)。与同龄对照组相比,新生和幼年模型组大鼠海马及前额皮层组织中NRG1、ErbB4表达水平显著升高(均P<0.05)。与新生模型组相比,幼年及成年模型组大鼠海马及前额皮层组织中NRG1、ErbB4表达水平显著降低,幼年模型组低于成年模型组(均P<0.05)。结论:抑郁可影响SD认知功能,降低其学习及记忆能力,脑发育早期抑郁对认知功能的损害更为明显,海马区及前额皮层NRG1、ErbB4的高表达可能是抑郁影响认知、学习和记忆功能的机制之一。

Objective:To study the expression of NRG1 and its receptor ErbB4 in different brain regions at different developmental stages and its relationship with cognitive function in depressed rats.Methods:Twenty newborn rats(15 days after birth),twenty young rats(30 days after birth)and twenty adult rats(90 days after birth)were randomly divided into control group and model group with 10 each.The depression model was established by chronic unpredictable mild stress(CUMS).The general situation of rats was observed.Open field experiment(OFT)was used to test the autonomous activity of rats.Morris water maze navigation test and space exploration test were used to evaluate the learning and memory function of rats.RT-PCR was used to detect the expression of NRG1 and ErbB4 genes in hippocampus and prefrontal cortex.Results:Compared with the same age control group,the weight of the newborn,young and adult model rats decreased significantly(all P<0.05).Compared with the same age control group,the scores of horizontal movement and vertical movement in the newborn model group and the young model group were significantly lower(all P<0.05).Compared with the newborn model group,the scores of horizontal movement and vertical movement in the young and adult model groups were significantly increased,and the scores in the adult model group were higher than those in the young model group(all P<0.05).Compared with the same age control group,the escape latency and swimming distance of the rats in the newborn model group and the young model group increased significantly,and the number of crossing platform decreased significantly(all P<0.05).Compared with the newborn model group,the escape latency and swimming distance of the young and adult model group were significantly reduced,the number of crossing platform in the young model group was significantly higher than that in the adult model group,and the number of crossing platform in the young model group was significantly lower than that in the adult model group(all P<0.05).Compared with the same age control group,NRG1 and ErbB4 expression levels in hippocampus and prefrontal cortex of newborn and young model rats were significantly higher(all P<0.05).Compared with the newborn model group,the expression levels of NRG1 and ErbB4 in the hippocampus and prefrontal cortex of the newborn and young model group were significantly lower than those of the adult model group(all P<0.05).Conclusion:Depression can affect the cognitive function of SD rats,reduce their learning and memory ability.Depression in the early stage of brain development has more obvious damage to cognitive function.The high expression of NRG1 and ErbB4 in hippocampus and prefrontal cortex may be one of the mechanisms of depression affecting cognitive,learning and memory function.