Objective To explore the effects of acute and chronic dizocilpine (MK-801) exposure on the expression of microRNA(miR)-181b, a schizophrenia-associated microRNA, in the frontal cortex of mouse brain and its potential role in the pathogenesis of schizophrenia. Methods In the acute experiment, forty mouse were divided into four groups randomly, the MK-801 and control groups were given intraperitoneal injection of different doses of MK-801 (0.125 mg/kg, 0.25 mg/kg and 0.5 mg/kg) and vehicle, respectively. In the chronic experiment, twenty-two mice were divided into two groups randomly. Mice were given vehicle or MK-801 (0.25 mg/kg per day) for 14 d. Quantitative real-time PCR technique was then used to detect the relative expression levels of miR-181b in the frontal cortex at 15 min after treatment in acute experiment or at 15 min after last injection on 14th day in chronic experiment. Results In the acute MK-801 administration groups, relative expression levels of miR-l81b were 1.00 ± 0.13 in control group, 0.65 ± 0.05 in 0.125 mg/kg group, 0.61 ± 0.05 in 0.25 mg/kg group, and 0.91 ± 0.08 in 0.5 mg/kg group, respectively. MiR-181b expression levels significantly decreased in MK 0.125 mg/kg and MK 0.25 mg/kg groups while remained unchanged in 0.5 mg/kg group compared to the control group. In the chronic MK-801 administration group, relative expression level of miR-181b significantly increased compared to the control group (1.86 ± 0.19 vs. 1.00 ± 0.10, P < 0.05). Conclusion There are different effects of acute and chronic administration rnof MK-801 on miR-181b in the mouse frontal cortex, indicating that miR-181b may play different roles in the acute and chronic mouse models of schizophrenia.%目的 研究急慢性注射地卓西平马来酸盐(MK-801)对小鼠额叶中与精神分裂症相关的微小RNA(microRNA,miRNA)-181b表达的影响,探讨其参与精神分裂症病理学的可能机制.方法 急性注射实验中40只小鼠随机分成四组,分别腹腔注射不同剂量(0.125 mg/k g,0.25 mg/kg,0.50 mg/kg)的MK-801和生理盐水(简称急性对照组),15 min后用实时荧光定量PCR (real-time PCR)技术检测额叶miRNA- 181b的相对表达量;慢性注射实验中22只小鼠随机分成两组,分别腹腔注射0.25 mg·kg-1·d-1的MK-801和生理盐水(简称慢性对照组),连续14 d,然后检测miRNA-181b的相对表达量.结果 急性注射0.125 mg/kg、0.25 mg/kg、0.50mg/kgMK-801的各组小鼠额叶miRNA-181b的相对表达水平分别为0.65±0.05、0.61±0.05和0.91±0.08.前两个剂量组miRNA-181b的表达明显低于对照组(1.00±0.13),P＜0.05,而0.5 mg/kg的MK-801则对miRNA-181b表达无影响(P＞0.05).慢性MK-801注射组miRNA-181b的相对表达量为1.86±0.19,显著高于慢性对照组(1.00±± 0.10),P＜0.05.结论 急性和慢性MK-801对额叶中miRNA-181b表达的影响不同,结合miR-181b的分子功能,提示miRNA-181b在急性和慢性模型鼠的构建中起到不同的作用.
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