CDK5在吗啡依赖诱导神经细丝蛋白过度磷酸化中的作用  

Role of CDK5 in Morphine Dependence-induced Neurofilament Hyperphosphorylation

作　　者：刘付宁[1] 纪风涛[1] 曹铭辉[1] 刘玲[1] 吴强[1] 梁建军[1] 

机构地区：[1]中山大学附属第二医院麻醉科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2010年第3期445-447,共3页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(7001595)

摘　　要：【目的】探讨吗啡依赖小鼠大脑皮质细胞周期依赖性蛋白激酶-5(CDK5)与蛋白磷酯酶-2A(PP-2A)变化及其对神经细丝蛋白磷酸化的作用。【方法】雄性昆明小鼠28只,随机等分为对照组、吗啡依赖组、roscovitine(CDK5选择性拮抗剂)预处理组和脑室注射对照组;除对照组外所有小鼠皮下注射吗啡5mg·kg-·1d-1,连续6d;roscovitine预处理组于每次皮下注射吗啡30min前予roscovitine预处理。免疫印迹法检测神经细丝蛋白磷酸化水平、p-CDK5(Ser159)和PP-2A表达水平。【结果】在吗啡依赖小鼠前额叶皮质,p-CDK5(Ser159)表达增加,神经细丝蛋白过度磷酸化;应用CDK5的选择性抑制剂roscovitine预处理后,p-CDK5(Ser159)表达减少,神经细丝蛋白磷酸化水平降低;各组间PP-2A表达水平差异无统计学意义。【结论】CDK5活性失调可能诱导吗啡依赖小鼠神经细丝蛋白过度磷酸化。【Objective】To investigate the changes of cyclin-dependent kinase-5（CDK5）and protein phosphatase-2A（PP-2A）,and the effects of them on neurofilament hyperphosphorylation in the cortex of morphine dependence mice.【Methods】Twenty-eight Kunming mice,male and weighing 20-25 g,were randomly divided into control group,morphine dependence group,roscovitine preconditioning group,and vehicle group with 7 mice each.Animals in morphine dependence group,roscovitine preconditioning group,and vehicle group were administered with morphine by subcutaneous injection of morphine 5 mg/kg/d for 6 d.The mice in roscovitine preconditioning group were administered with roscovitine（30 nmoL/mouse）intracerebroventricularly（i.c.v.）30 min before treatment with morphine.The mice in vehicle group were administered with vehicle i.c.v.30 min before treatment with morphine.All the animals were sacrificed to get the prefrontal cortex for detecting the level of neurofilament hyperphosphorylation,p-CDK5（Ser159）,and PP-2A with immunoblotting 12 h after the last injections,respectively.【Results】（1）Compared with control group,the level of phosphorylated neurofilament was enhanced,and the level of p-CDK5（Ser159）was increased in morphine dependence group.（2）Compared with vehicle group,the level of phosphorylated neurofilament was reduced,and the level of p-CDK5（Ser159）was decreased in roscovitine preconditioning group.（3）The level of PP-2A was found unaltered in all groups.【Conclusion】Disturbance of cyclin-dependent kinase 5 induced neurofilament hyperphosphorylation in morphine dependence mice brain.

关 键 词：吗啡依赖 神经细丝 磷酸化 CDK5 

分 类 号：R749.611[医药卫生—神经病学与精神病学]