Potashkin Judith A, Kang Un Jung, Loomis Patricia A, Jodelka Francine M, Ding Yunmin, Meredith Gloria E
Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Brain Res. 2007 Nov 28;1182:1-10. doi: 10.1016/j.brainres.2007.08.080. Epub 2007 Sep 14.
Most cases of Parkinson's disease (PD) are sporadic, suggesting an environmental influence on individuals affected by this neurodegenerative disorder. Environmental stresses often lead to changes in the regulation of splicing of pre-mRNA transcripts and this may lead to the pathogenesis of the disease. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model was used to examine the changes in the splicing of the fosB and rgs9 transcripts. The ratio of DeltafosB/fosB transcript was decreased in the substantia nigra and unchanged in the striatum after acute MPTP treatment. The DeltafosB/fosB transcript ratio decreased initially and then increased in the striatum of chronically MPTP-treated animals due to different degrees of reduction for the splice variants over time, whereas the ratio was unchanged in the substantia nigra. The ratio of rgs9-2/rgs9-1 transcript decreased in the substantia nigra of mice after acute MPTP treatment and increased temporarily in the striatum after chronic MPTP treatment. There was an increase in the DeltaFosB/FosB and RGS9-2/RGS9-1 protein ratios 3 weeks and 3 days post-treatment, respectively, in chronically treated mice. The data indicate that the pattern of splice isoforms of fosB and rgs9 reflects the brain's immediate and long-term responses to the physiological stress associated with Parkinsonism.
大多数帕金森病（PD）病例是散发性的，这表明环境因素会影响受这种神经退行性疾病影响的个体。环境压力常常导致前体信使核糖核酸（pre-mRNA）转录本剪接调控的变化，这可能会导致疾病的发病机制。使用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）/丙磺舒小鼠模型来研究fosB和rgs9转录本剪接的变化。急性MPTP处理后，黑质中DeltafosB/fosB转录本的比例降低，纹状体中该比例未变。在长期接受MPTP处理的动物的纹状体中，由于剪接变体随时间不同程度的减少，DeltafosB/fosB转录本比例最初降低，然后升高，而在黑质中该比例未变。急性MPTP处理后，小鼠黑质中rgs9-2/rgs9-1转录本的比例降低，慢性MPTP处理后，纹状体中该比例暂时升高。在长期处理的小鼠中，处理后3周和3天，DeltaFosB/FosB和RGS9-2/RGS9-1蛋白比例分别增加。数据表明，fosB和rgs9的剪接异构体模式反映了大脑对与帕金森症相关的生理应激的即时和长期反应。
