早期母爱剥夺对青春期大鼠抑郁样行为及海马区颗粒层神经发生的影响

Effect of early-life maternal deprivation on depressive-like behavior and neurogenesis in hippocampal granular layer of adolescent rat

目的探讨早期母爱剥夺对青春期(6~7周龄)大鼠抑郁样行为及海马区颗粒层神经发生的影响。方法采用随机数字表法将新生大鼠根据窝别随机分为母爱剥夺组和对照组,每组3窝。母爱剥夺组幼鼠出生后第1~14天给予母爱剥夺应激,对照组幼鼠与母鼠同笼,正常饲养。记录大鼠5~6周龄时的体质量增量,6周龄后进行糖水偏爱实验,随后处死大鼠取脑,采用免疫荧光染色观察大鼠海马区颗粒层Ki67和巢蛋白(Nestin)阳性细胞形态及数目改变。采用SPSS 22.0进行统计分析,两组数据经检验符合正态分布后进行t检验。结果两组大鼠5~6周龄时的体质量增长量差异有统计学意义,母爱剥夺组大鼠体质量增长量[(20.57±2.19)g]低于对照组[(30.57±1.25)g](t=3.96,P<0.01),糖水偏爱率[(58.38±3.14)%]明显低于对照组[(73.88±3.67)%](t=3.21,P<0.01)。免疫荧光结果显示,母爱剥夺组大鼠海马区颗粒层Ki67免疫阳性细胞数少于对照组[(5.13±0.31)个,(7.60±0.38)个,t=5.09,P<0.01],Nestin免疫阳性细胞数多于对照组[(16.65±0.79)个,(7.64±0.70)个,t=8.51,P<0.01],且母爱剥夺组大鼠Nestin免疫阳性细胞胞体发出突起分枝较多,形态与星形胶质细胞相似,而对照组免疫阳性细胞发出突起较少,胞体呈椭圆形。结论母爱剥夺应激可造成青春期大鼠出现抑郁样行为,这可能与母爱剥夺应激致其海马区颗粒层新生神经元数量减少、Nestin免疫阳性的激活态星形胶质细胞大量出现相关。

Objective To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats(6-7 weeks old).Methods Neonatal rats were randomly divided into maternal deprivation group and control group,with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old,the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution,and then t-test was carried out.Results There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group,rats in the maternal deprivation group had lower body weight growth((20.57±2.19)g,(30.57±1.25)g,t=3.96,P<0.01))and lower sucrose preference rate((58.38±53.14)%,(73.88±3.67)%,t=3.21,P<0.01).The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group((5.13±0.31),(7.60±0.38),t=5.09,P<0.01),and the number of Nestin immunofluorescence positive cells was more than that in the control group((16.65±0.79),(7.64±0.70),t=8.51,P<0.01).The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches,and the morphology was similar to astrocytes,while the immunofluorescence positive cells in the control group had fewer protrusions,and the cell body was oval.Conclusions Early-life maternal deprivation leads to depressive-like behavior in adolescent rats,which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.