条件性敲除Med23基因对成年小鼠海马新生神经元及行为的影响

Effects of conditioned knockout Med23 gene on neonatal neurons and behavior in hippocampus of adult mice

目的:观察条件性敲除中介体亚单位23(Med23)基因对小鼠海马神经发育和行为的影响。方法:利用灌胃方法给予Med23 CKO小鼠他莫昔芬(TAM),通过括旷场实验、悬尾实验和黑白箱实验检测检测小鼠的行为,利用免疫荧光染色检测小鼠海马5-溴-2-脱氧尿苷(BrdU)、mKi-67基因编码核蛋白(Ki67)、微小染色体维持蛋白2(MCM2)、双皮质素(DCX)和神经源性分化因子(NeuroD)的表达。结果:与WT小鼠相比,Med23 CKO小鼠中间静息时间明显缩短(P<0.05),进入白箱的潜伏期明显延长(P<0.05),穿越到白箱的次数明显减少(P<0.05),在白箱停留的时间明显缩短(P<0.05);Med23 CKO小鼠海马BrdU、Ki67、MCM2表达均减少(P<0.05),DCX和NeuroD阳性细胞数也明显减少。结论:Med23参与调节小鼠海马神经化生,海马Med23缺失会导致小鼠出现焦虑及抑郁行为。

Objective:To observe the effects of conditional knockout of mediator subunit 23(Med23)gene on hippocampal neural development and behavior of mice.Methods:Med23 CKO mice were given tamoxifen(TAM)by gavage.The behavior of mice was detected by open field test,tail suspension test,and black and white box test.The expressions of 5-bromo-2-deoxyuridine(BrdU),mKi-67 gene coding nucleoprotein(Ki67),microchromosome maintenance protein(MCM2),microtubule-associated protein(DCX),and neurogenic differentiation factor(NeuroD)in the hippocampus of mice were detected by immunofluorescence staining.Results:Compared with WT mice,Med23 CKO mice had significantly shorter resting time,longer incubation period into the white box,fewer times of crossing to the white box and shorter stay time in the white box(P<0.05).The expressions of BrdU,Ki67,and MCM2 in hippocampus of Med23 CKO mice were significantly decreased(P<0.05).What’s more,the number of DCX and NeuroD positive cells were also significantly decreased compared with Med23 CKO mice(P<0.05).Conclusion:Med23 is involved in the regulation of hippocampal neurometaplasia in mice,and the loss of Med23 in hippocampus can lead to anxiety and depression in mice.