多动症大鼠前额叶皮质中Nf1对BDNF的调节作用

Nf1 and BDNF Dysregulation in the Prefrontal Cortex Involved in the Pathogenesis of Attention Deficit Hyperactivity

目的探讨神经纤维素(neurofibromin 1,Nf1)对脑源性神经营养因子(BDNF)表达的调节在多动症(ADHD)发病机制中的作用。方法选用SHR大鼠作为多动症动物模型,WKY大鼠作为对照。应用RT-PCR、蛋白印记法检测Nf1和BDNF的mRNA、蛋白质水平;将Nf1过表达质粒共转染至PC12H及7919细胞,检测Nf1过表达后BDNF水平以探索Nf1与BDNF作用关系;用Image-pro Plus软件进行定量分析。结果与WKY大鼠相较,SHR动物模型脑前额叶皮质中Nf1、BDNF水平均偏低(P=0.000);过表达Nf1可使BDNF水平上调(PC12H细胞P=0.000,7919细胞P<0.05)。结论 SHR前额叶皮质中Nf1、BDNF水平偏低,Nf1对BDNF有正性调控作用。前额叶皮质中Nf1对BDNF的调控作用可能参与多动症的发病机制。

Objective To investigate the interaction between the Nf1 （Neurofibromin 1）and the BDNF （brain derived neurotrophic factor） in the mechanism of attention deficit hyperactivity disorder （ADHD）.Methods Spontaneously hypertensive rats were chosen as the experimental group and WKY servesd as control. RT-PCR, Western-blot were used to detect the mRNA and protein expression levels of Nf1 and BDNF. To explore their relationship, BDNF expression levels were detected after Nf1 expression plasmid transferred and transfection in PC12H and CBRH-7919 cells.Results were quantified by Image-pro plus software.Results In the PFC of ADHD model rats SHR, Nf1 expression was abnormally degressive（P=0.000）, in common with the expression of BDNF（P=0.000）. Ectopic expression of Nf1 further encouraged the expression of BDNF （PC12H：P=0.000,7919：P〈0.05）.Conclusion Nf1 expression was significantly lower in PFC of SHR than control, and positively correlated with the levels of BDNF. These findings show that in the prefrontal cortex, Nf1-BDNF dysregulation may be involved in the pathomechanism of ADHD.