Combined treatment with C16 peptide and angiopoietin-1 confers neuroprotection and reduces inflammation in 3-nitropropionic acid-induced dystonia mice.
Combined treatment with C16 peptide and angiopoietin-1 confers neuroprotection and reduces inflammation in 3-nitropropionic acid-induced dystonia mice.
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C16肽和血管生成素-1联合治疗对3-硝基丙酸诱导的肌张力障碍小鼠具有神经保护作用，并能减轻炎症。
DOI：
10.18632/aging.203354
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发表时间：
2021-07-29
期刊：
影响因子：
--
通讯作者：
Han S
中科院分区：
文献类型：
--
作者：
Fu XX;Cai HY;Jiang H;Han S
肌张力障碍是一种与许多大脑区域的异常相关的疾病，包括基底节和小脑。毒素3-硝基丙酸(3-NP)可诱导小鼠纹状体和黑质的神经病理，包括兴奋性毒性、神经炎症和广泛的神经元萎缩，其特征是进行性运动功能障碍、肌张力障碍和记忆丧失，与人类观察到的相似。我们通过注射3-NP建立了小鼠肌张力障碍模型。鉴于已报道的内皮生长因子血管生成素-1(Ang-1)和抗炎整合素αvβ3结合肽C16的神经保护作用，本研究利用在体小鼠模型，用多种方法评价了它们对3-NP纹状体毒性的联合作用及其治疗潜力。将60只小鼠随机等分为3组：对照组、3-NP组和3-NP+C16+Ang-1组。进行行为学和电生理测试，观察C16+Ang-1联合治疗对神经功能恢复的影响。我们发现，C16+Ang-1治疗减轻了3-NP诱导的中枢神经系统的行为、生化和细胞变化，并通过恢复血管通透性和减轻微环境中的炎症而促进功能恢复。总之，我们的结果证实了C16+Ang-1联合治疗的神经保护作用，并提示它们有可能作为3-NP诱导的肌张力障碍的补充治疗。
Dystonia is a disorder associated with abnormalities in many brain regions including the basal ganglia and cerebellum. The toxin 3-Nitropropionic acid (3-NP) can induce neuropathologies in the mice striatum and nigra substance, including excitotoxicity, neuroinflammation, and extensive neuronal atrophy, characterized by progressive motor dysfunction, dystonia, and memory loss, mimicking those observed in humans. We established a mouse model of dystonia by administering 3-NP. Given the reported neuroprotective effects of the endothelial growth factor angiopoietin-1 (Ang-1) and the anti-inflammatory integrin αvβ3 binding peptide C16, we performed this study to evaluate their combined effects on 3-NP striatal toxicity and their therapeutic potential with multiple methods using an in vivo mouse model. Sixty mice were equally and randomly divided into three groups: control, 3-NP treatment, and 3-NP+C16+Ang-1 treatment. Behavioral and electrophysiological tests were conducted and the effect of the combined C16+Ang-1 treatment on neural function recovery was determined. We found that C16+Ang-1 treatment alleviated 3-NP-induced behavioral, biochemical, and cellular alterations in the central nervous system and promoted function recovery by restoring vascular permeability and reducing inflammation in the micro-environment. In conclusion, our results confirmed the neuroprotective effect of combined C16+Ang-1 treatment and suggest their potential as a complementary therapeutic against 3-NP-induced dystonia.
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