NMDA受体NR2B基因对海马成年新生神经元生存的影响

The Role of NR2B-containing NMDA Receptors in Selective Survival in the Hippocampal Adult-born Neurons

目的:研究NMDA受体NR2B基因对海马成年新生神经元生存的影响。方法:通过Cre-loxp重组酶系统构建NMDA受体NR2B亚型基因单细胞敲除模型。观察NR2B基因敲除神经元的存活情况及其形态发生。结果:在逆转录病毒注射后7、17、28、56 d,NR2Bfl/fl小鼠中,成年海马新生神经元生存比例在各观察时间点一致,与同组野生型神经元无显著性差异。NR2B基因敲除神经元神经元大体形态分化发育与野生型神经元类似,但在17、28 d时顶端树突上的棘突发生显著减少(P<0.01)。结论:NMDA受体NR2B亚型基因敲除对海马成年新生神经元生存无显著性影响,但可影响突触发生。

Objective： To investigate the effects of conditional NR2B knock out on selective survival of the adult-born granule cells generated fi＇om subgranule zone （SGZ） in the hippocampus. Methods： Using retroviral genetic labeling approaches to mark the adult born neurons with GFP/Cre, the survival of the adult born neurons was evaluated by the ratio of Cre＋/Cre granule cells at different time points after viral injection in both the WT and NR2Ba transgenic mice. The development of the newborn neurons was also observed. Results： The ratio of the Cre＋/Cre granule cells in the dentate gyms was constant in the both WT and NR2B^rfl/ti transgenic mice at all the time points. Meanwhile, there was no statistical difference in survival ratio between the different genotypes （WT and NR2B^tl/tl mice） at each time point. The development of the NR2B-depletion neurons is similar to that in the WT neurons, however synaptogenesis was reduced significantly at 17 and 28 dpi （P〈0.01）. Conclusion： NR2B-containing NMDA receptors are not required for selective survival of the hippocampal adult born granule cells, but for the synaptogenesis.