The expression of miR-133b in the brain of methamphetamine dependent rats and its regulation on neuronal toxic injury / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the expression of miR-133b in the brain of methamphetamine(MA) dependent rats and its regulatory effects on neuronal toxic injury.MethodsThrough continuous intraperitoneal injection to rats with MA(10 mg/kg),the conditioned place preference(CPP) rats model was established,and the expression of miR-133b in the cerebral cortex of model rats was detected by real-time fluorescence quantitative PCR(RT-PCR).PC12 cells were cultured in vitro and treated with MA(800 μmol/L),and then miR-133b expression in cultured neurons was detected.miR-133b mimics and inhibitor were transfected to PC12 cells respectively to observe the effect of miR-133b on the mitochondrial membrane potential(MMP) of cultured neurons.ResultsAfter continuous intraperitoneal injection with MA for 14 days,the residence time of rats in the box with medicine((620.20±44.80)s) was significantly longer compared with the control group((341.80±25.12)s,P<0.01),which showed that MA dependent rats model was successfully established.The RT-PCR detection results showed that the expression of miR-133b in the cerebral cortex of model rats(0.36±0.05) significantly decreased compared with the control group(0.99±0.08,P<0.01).In the in vitro model,most of the neuronal cell bodies became round and the neuorites were withdrawn after MA treatment.Compared with the control group(1.00±0.02),the RT-PCR detection results showed that the expression of miR-133b in MA group(0.74±0.05) decreased(P<0.05).The JC-1 detection results showed that the MMP of the MA group(109.85±7.03) decreased significantly contrast to the control group(36.49±3.89,P<0.01),the MMP of the miR-133b mimics group(58.97±6.56) increased significantly contrast to the mimics control group(135.46±15.04,P<0.01) and the MMP of the miR-133b inhibitor group(162.84±14.15) decreased contrast to the inhibitor control group(139.81±12.26,P<0.05).ConclusionsThe expression of miR-133b in the cerebral cortex of MA dependent rats and in vitro neuron model treated with MA are significantly downregulated.By regulating the expression of miR-133b,the MMP damage of cultured neurons treated with MA is changed,indicating that miR-133b is not only involved in the nerve injury induced by MA,but also possiblely as a molecular target for intervention.