Ndrg2对成年大鼠皮层机械性损伤后神经发生的影响

目的:探讨Ndrg2对成年大鼠皮层机械损伤后神经发生的影响及可能作用机制。方法:选取成年雄性Sprague-Dawley大鼠24只,利用立体定位法对大鼠皮层进行针刺机械损伤。随后分为4组(n=6):对照组(注射生理盐水)、病毒对照组(注射空载体病毒)、上调Ndrg2组(注射AAV-Ndrg2病毒)及抑制剂组(注射AAV-Ndrg2病毒和-分泌酶抑制剂DAPT)。术后7 d免疫荧光检测损伤区周边Ndrg2及Nestin表达变化。结果:在对照组和病毒对照组,针道周边的Ndrg2+细胞明显增多,并表达神经干细胞标记物Nestin;与病毒对照组相比,上调Ndrg2组的Ndrg2+及Ndrg2+/Nestin~+细胞进一步增多(P0.01);注射Notch信号抑制剂DAPT后,与上调Ndrg2组相比,针道周边Nestin~+细胞数目明显减少(P0.01),但Ndrg2+细胞数目无明显改变(P0.05)。结论:大鼠皮层机械损伤后,Ndrg2可参与损伤区的神经发生过程;Notch信号通路可能在Ndrg2促神经发生中发挥关键作用。

Involvement of Ndrg2 in the neurogenesis of adult rat cortex after traumatic injury

Objective:To study whether Ndrg2 is involved in the neurogenesis of adult rat cortex after traumatic injury,and to explore possible underlying mechanisms.Methods:Twenty-four male Sprague-Dawley rats were subjected to the stab injurywitha needle by a stereotaxic method,and then randomly divided into four groups:two control groups (control group and virus control group,which were administrated with saline and virus empty vector by intracerebroventricular injection (i.c.v.),respectively),and two experimental groups (Ndrg2 over-expression group and antagonist group,which were injected i.c.v.with AAV-Ndrg2 virus and AAV-Ndrg2 virus plus-secretase inhibitor DAPT,respectively).Ndrg2-or Nestin-(a neural stem cell marker) expressing cells were detected in the boundary of lesion area by immunolluorescent stain at 7dafter stab injury.Results:In the control group and virus control group,the number of Ndrg2 + cells at the lesion boundary was obviously increased,and these cells also expressed Nestin;Compared withthe virus control group,the numbers of Ndrg2 + cells and Ndrg2 +/Nestin+ cells were further increased (P ＜0.01) in the Ndrg2 overexpression group;After treated with Notch signaling antagonist DAPT,the number of Nestin + cells was significantly decreased (P ＜ 0.01).However,DAPT did not affect the number of Ndrg2 + cells (P ＞ 0.05).Conclusion:Ndrg2 could be involved in the cortical neurogenesis at the lesion boundary after injury,and Notch signaling pathway may play a key role in this process.