An angiogenic inhibitor, cyclic RGDfV, attenuates MPTP-induced dopamine neuron toxicity.
An angiogenic inhibitor, cyclic RGDfV, attenuates MPTP-induced dopamine neuron toxicity.
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DOI：
10.1016/j.expneurol.2011.06.004
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发表时间：
2011-09
影响因子：
5.3
通讯作者：
Hendey, Bill
中科院分区：
文献类型：
--
作者：
Patel, Aditiben;Toia, Giuseppe V.;Colletta, Kalea;Bradaric, Brinda Desai;Carvey, Paul M.;Hendey, Bill
关键词：
我们以前证明，几种多巴胺（DA）神经毒素产生的斑点状领域的FITC标记的白蛋白（FITC-LA）泄漏黑质和纹状体表明血脑屏障（BBB）功能障碍。此外，这种渗漏与αvβ3整合素上调（血管生成的标志物）共定位。这表明FITC-LA泄漏可能是血管生成的结果。为了评估血管生成在DA神经元损失中的可能作用，我们用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理小鼠，并在第二天用cyRGDfV（一种与整合素αvβ3结合并阻止血管生成的环肽）处理。治疗后3天（b.i.d.）cyRGDfV阻断了MPTP诱导的整合素β3免疫反应性（血管生成的标志物）的上调、FITC-LA向脑实质中的渗漏（BBB破坏的标志物）以及Zona Occludin-1（ZO-1;紧密连接完整性的标志物）的下调。此外，cyRGDfV还完全防止酪氨酸羟化酶免疫反应性细胞损失（DA神经元的标志物），并显着减弱激活的小胶质细胞（Iba 1细胞计数和形态）的上调。这些数据表明，cyRGDfV，也许还有其他抗血管生成药物，在急性MPTP治疗后具有神经保护作用，并可能表明代偿性血管生成和BBB功能障碍可能导致炎症和DA神经元丢失。
We previously demonstrated that several dopamine (DA) neurotoxins produced punctate areas of FITC-labeled albumin (FITC-LA) leakage in the substantia nigra and striatum suggesting blood brain barrier (BBB) dysfunction. Further, this leakage was co-localized with αvβ3 integrin up-regulation, a marker for angiogenesis. This suggested that the FITC-LA leakage might have been a result of angiogenesis. To assess the possible role of angiogenesis in DA neuron loss, we treated mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) and on the following day treated with cyRGDfV, a cyclic peptide that binds to integrin αvβ3 and prevents angiogenesis. Post-treatment for three days (b.i.d.) with cyRGDfV blocked the MPTP-induced upregulation of integrin β3 immunoreactivity (a marker for angiogenesis), leakage of FITC-LA into brain parenchyma (a marker for BBB disruption) as well as the down regulation of Zona Occludin-1 (ZO-1; a marker for tight junction integrity). In addition, cyRGDfV also completely prevented tyrosine hydroxylase immunoreactive cell loss (a marker for DA neurons) and markedly attenuated the up-regulation of activated microglia (Iba1 cell counts and morphology). These data suggest that cyRGDfV, and perhaps other anti-angiogenic drugs, are neuroprotective following acute MPTP treatment and may suggest that compensatory angiogenesis and BBB dysfunction may contribute to inflammation and DA neuron loss.
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影响因子：
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作者：
Baluk, P;Lee, CG;McDonald, DM
通讯作者：
McDonald, DM
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作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
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通讯作者：
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作者：
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通讯作者：
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