MPTP对C57BL/6J小鼠脑时钟基因mPer1 mRNA表达的影响

目的研究神经毒素1-甲基-4-苯基-1,2,3,6-四羟基吡啶(MPTP)对小鼠脑组织中时钟基因mPer1mRNA表达的影响。方法将C57BL/6J小鼠用计算机辅助法随机分为MPTP组和对照组,MPTP组腹腔注射MPTP-HCl,对照组注射0.9%氯化钠注射液,连续5d,第11天连续24h按6个时间点取材。用HPLC-ECD检测纹状体中多巴胺(DA)含量,用实时定量RT-PCR检测纹状体和其余脑组织mPer1 mRNA水平。结果MPTP组纹状体DA水平较正常对照组减少了80%,并维持低水平长达10d;纹状体mPer1mRNA在24h内呈明显节律性变化,而其余脑组织mPer1 mRNA无明显节律性变化;MPTP处理导致纹状体和其余脑组织mPer1 mRNA水平增高及纹状体mPer1 mRNA表达高峰提前。结论MPTP引起小鼠纹状体时钟基因的表达水平和节律性发生改变,提示MPTP可能通过改变细胞内的节律控制中心而影响机体的生物节律。

Effect of MPTP on the mPer1 mRNA Expression in the Brain of C57BL/6J

Objective To study the mPer1 mRNA expression profiles in striatum and other brain regions in MPTP-treated mice. Methods Sixty C57 BL/6J male mice were randomized into MPTP and control groups. For MPTP group, MPTP-HCL was administered intraperitoneally in 5 consecutive days. For the control group, MPTP-HCL was replaced by same volume of saline. On the 11th day, mice were sacrificed at six different time points during a 24-hour periods, and striatum and the rest of brain regions were isolated. Dopamine levels of striatum were measured using HPLC-ECD. The mRNA expression of mPer1 was examined using real time PCR. Results The dopamine levels in striatum decreased about 80% in MPTP-treated mice, which remained at low level for up to 10 days. The expression of mPer1 mRNA in striatum increased significantly in MPTP-treated mice, with the rhythmic expression phase being shifted. Compared with control mice, the expression peak reached 4 hours earlier. The mPer1 mRNA expression in the rest of brain regions was also increased significantly in MPTP-treated mice, but no rhythmic changes occurred. Conclusion MPTP can change the mRNA expression of mPer1 in the striatum and the rest of brain regions, indicating that MPTP may affect the intracellular circadian oscillator in the brain.