Mechanism of over-activation in direct pathway mediated by dopamine D_1 receptor in rats with levodopa-induced dyskinesias  

作　　者：Xue-Bing CAO Qiang GUAN Yan XU Lan WANG Sheng-Gang SUN 

机构地区：[1]Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

出　　处：《Neuroscience Bulletin》2006年第3期159-164,共6页神经科学通报（英文版）

摘　　要：Objective To study the changes of prodynorphin （PDyn） gene expression and dopamine and cAMPregulated phosphoprotein of 32 kDa （DARPP-32） phosphorylation in rats with levodopa-induced dyskinesias （LID）, and to explore the mechanism of over-activation in direct pathway mediated by dopamine D1 receptor. Methods Parkinson＇s disease （PD） rats were received levodopa （10 mg/kg, i.p.） for 28 d to get the LID rats. According to the behavior scale, LID rats were divided into mild （n=8） and severe （n=16） groups. On day 29, 8 rats in severe LID group were given an acute intraperitoneal injection of MK-801 （0.1 mg/kg） 15 min before levodopa treatment （MK-801 group, n=8）. The normal rats received same course and dosage of levodopa as the control group （n=8）. Hybridization in situ was used to measure the expression of PDyn mRNA in striatum. Protein and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 level were measured by immunoblotting and RT-PCR, respectively. Results The levels of PDyn mRNA and phospho-Thr-34 DARPP-32 increased significantly in LID rats compared with control rats （P〈0.01）, and they also increased markedly in severe LID group compared with mild group （P〈0.01）. Conclusion Phospho-Thr-34 DARPP-32 level was increased in LID rats, which contributed to the over-activation of direct pathway mediated by dopamine D1 receptor.Objective To study the changes of prodynorphin （PDyn） gene expression and dopamine and cAMPregulated phosphoprotein of 32 kDa （DARPP-32） phosphorylation in rats with levodopa-induced dyskinesias （LID）, and to explore the mechanism of over-activation in direct pathway mediated by dopamine D1 receptor. Methods Parkinson＇s disease （PD） rats were received levodopa （10 mg/kg, i.p.） for 28 d to get the LID rats. According to the behavior scale, LID rats were divided into mild （n=8） and severe （n=16） groups. On day 29, 8 rats in severe LID group were given an acute intraperitoneal injection of MK-801 （0.1 mg/kg） 15 min before levodopa treatment （MK-801 group, n=8）. The normal rats received same course and dosage of levodopa as the control group （n=8）. Hybridization in situ was used to measure the expression of PDyn mRNA in striatum. Protein and mRNA levels of total DARPP-32 and phospho-Thr-34 DARPP-32 level were measured by immunoblotting and RT-PCR, respectively. Results The levels of PDyn mRNA and phospho-Thr-34 DARPP-32 increased significantly in LID rats compared with control rats （P〈0.01）, and they also increased markedly in severe LID group compared with mild group （P〈0.01）. Conclusion Phospho-Thr-34 DARPP-32 level was increased in LID rats, which contributed to the over-activation of direct pathway mediated by dopamine D1 receptor.

关 键 词：levodopa-induced dyskinesias PRODYNORPHIN Dopamine and cAMP-regulated phosphoprotein of 32 kDa 

分 类 号：R742.5[医药卫生—神经病学与精神病学]