Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Mediators Inflamm. 2013;2013:370526. doi: 10.1155/2013/370526. Epub 2013 Jun 19.
The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated.
本研究探讨了基质金属蛋白酶-3（MMP-3）是否参与了血脑屏障（BBB）损伤和外周免疫细胞浸润的 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病小鼠模型中黑质纹状体通路多巴胺能（DA）神经元的丢失。MPTP 处理小鼠脑切片的酪氨酸羟化酶（TH）免疫染色显示，MPTP 诱导了黑质纹状体 DA 神经元的显著退化。此外，FITC 标记的白蛋白检测和免疫染色显示，MPTP 导致 BBB 损伤，并增加了黑质中 ED-1 和 CD-3 免疫阳性细胞的数量。MMP-3 的基因缺失减少了黑质纹状体 DA 神经元的丢失，并改善了运动功能。MMP-3 缺失提供的这种神经保护作用与 BBB 破坏的抑制以及黑质中 ED-1 和 CD-3 免疫阳性细胞数量的减少有关。这些数据表明，MMP-3 可能在涉及 BBB 损伤和神经炎症的神经退行性疾病（如 PD）中发挥关键作用。
