MMP-3 contributes to nigrostriatal dopaminergic neuronal loss, BBB damage, and neuroinflammation in an MPTP mouse model of Parkinson's disease.
MMP-3 contributes to nigrostriatal dopaminergic neuronal loss, BBB damage, and neuroinflammation in an MPTP mouse model of Parkinson's disease.
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DOI：
10.1155/2013/370526
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发表时间：
2013
影响因子：
4.6
通讯作者：
Jin BK
中科院分区：
文献类型：
--
作者：
Chung YC;Kim YS;Bok E;Yune TY;Maeng S;Jin BK
本研究在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）小鼠血脑屏障（BBB）损伤和外周免疫细胞浸润的帕金森病模型中，研究基质金属蛋白酶-3 （MMP-3）是否参与黑质纹状体途径多巴胺能（DA）神经元的丢失。MPTP处理小鼠脑切片酪氨酸羟化酶（TH）免疫染色显示MPTP诱导黑质纹状体DA神经元显著变性。此外，fitc标记白蛋白检测和免疫染色显示MPTP对血脑屏障造成损伤，并增加黑质（SN）中ED-1-和cd -3免疫阳性细胞的数量。基因消融MMP-3可减少黑质纹状体DA神经元的丢失，改善运动功能。MMP-3缺失所提供的这种神经保护作用与抑制血脑屏障破坏以及SN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可能在神经退行性疾病（如PD）中发挥关键作用，其中涉及血脑屏障损伤和神经炎症。
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.
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