早期社会隔离对雌性ICR小鼠焦虑水平、社会行为及神经内分泌的影响

Effects of Early Social Isolation on Anxiety Levels,Social Behaviors,and Neuroendocrine in Female ICR Mice

许多证据表明早期生活应激会影响动物成年后的行为和神经化学改变,然而该过程的机制还不完全清楚。脑源性神经营养因子(BDNF)、催产素(OT)和糖皮质激素受体(GR)参与对应激的神经适应性反应。本实验将出生3 d后的雌性ICR小鼠幼仔每日隔离3 h直至出生21 d,在60日龄时检测其焦虑水平、社会行为及血清中皮质酮(CORT)和OT的水平,同时检测了中枢BDNF、OT和GR的阳性神经元表达。结果表明,与对照组相比,早期隔离组小鼠的焦虑水平增加,运动性和社会行为减少,同时血清中CORT水平上升、海马CA1和CA2/3区的BDNF及GR的阳性神经元表达下降,下丘脑室旁核和视上核的OT阳性神经元表达减少。这些结果表明,早期社会隔离下调了BDNF、OT和GR的水平,并通过调制应激系统影响雌性ICR小鼠的情绪与社会行为。

Accumulating evidence showed that early life stress induces significant behavioral and neurochemical changes in adulthood. However,the mechanisms of this process are not well understood. Brain-derived neurotrophic factor（ BDNF）,oxytocin（ OT） and glucocorticoid receptor（ GR） are implicated in the neuroadaptational response to stress. In this study,female ICR mice pups were subjected to repeated separation 3 h per day from postnatal day（ PND） 3 to PND 21. On PND 60,the anxiety levels,social behaviors,serum corticosterone（ CORT） and OT were assessed,while the expression of BDNF-,OT- and GR-immunoreactive（ ir） neurons were also examined. The results showed that early social isolation enhanced anxiety levels and resulted in a reduction in locomotion and social behaviors compared to the control. Along with these changes,isolation treatment significantly up-regulated the levels of CORT in serum,and decreased the BDNF-ir and GR-ir expression in the CA1 and CA2 /3 of the hippocampus,as well as OT-ir expression in the paraventricular nucleus and supraoptic nucleus. These findings demonstrated that early social isolation down-regulated the levels of BDNF,OT and GR,which were involved in mediating the stress system to affect emotion and social behaviors.