Kang Jun Mo, Jung Jae-Chul, Kim Heejeong, Lim Heena, Jang Soyong, Oh Seikwan
Department of Neuroscience and Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, 158-710, Korea.
Arch Pharm Res. 2008 Sep;31(9):1098-107. doi: 10.1007/s12272-001-1275-5. Epub 2008 Sep 20.
In this study, we investigated the neuroprotective effect of a benzylideneacetophenone derivative, JC3, in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD). C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. JC3 (10 mg/kg, i.p.) treatment was initiated 2 h after the first administration of MPTP and then at 24-h intervals for 3 consecutive days. The mice were sacrificed for analyses 7 days after the last MPTP injection. Immunohistochemistry and Western blot were used to determine the expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), OX-42 (a marker of microglial activation), and glial fibrillary acid protein (GFAP, a marker of astrocyte activation) in the substantia nigra (SN) and striatum (ST). The results of these experiments demonstrated that JC3 restored the decreased TH-immunoreactivity (IR) and DAT and JC3 attenuated the increase in OX-42, GFAP, and COX-2 on the SN and ST on day 7 post-MPTP injection. These results suggest that JC3 can be a neuroprotective agent in an MPTP-induced model of PD.
在本研究中,我们在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠模型中研究了苯亚甲基苯乙酮衍生物JC3的神经保护作用。C57BL/6小鼠连续5天腹腔注射MPTP(30 mg/kg)。在首次注射MPTP后2小时开始腹腔注射JC3(10 mg/kg),然后连续3天每隔24小时注射一次。在最后一次注射MPTP后7天处死小鼠进行分析。采用免疫组织化学和蛋白质免疫印迹法测定黑质(SN)和纹状体(ST)中酪氨酸羟化酶(TH)、多巴胺转运体(DAT)、OX-42(小胶质细胞活化标志物)和胶质纤维酸性蛋白(GFAP,星形胶质细胞活化标志物)的表达水平。这些实验结果表明,在MPTP注射后第7天,JC3恢复了降低的TH免疫反应性(IR)和DAT,并且JC3减弱了SN和ST中OX-42、GFAP和COX-2的增加。这些结果表明,JC3在MPTP诱导的PD模型中可能是一种神经保护剂。