Inserm, U1235, Nantes, France.
University Nantes, Nantes, France.
J Neurochem. 2019 Mar;148(6):746-760. doi: 10.1111/jnc.14656. Epub 2019 Jan 24.
The protein alpha-synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the CNS but also in the enteric nervous system (ENS). The growing body of evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of inflammation on alpha-synuclein expression in primary culture of rat ENS and in mice with dextran sulfate sodium-induced colitis. Using western blot and qPCR, we found that both lipopolysaccharide and a combination of tumor necrosis factor-α and interleukin 1-β decreased the expression levels of alpha-synuclein in primary culture of rat ENS, an effect that was prevented in the presence of the p38 inhibitors SB203580 and BIRB 796. Lipopolysaccharide and tumor necrosis factor-α/interleukin 1-β had no effect on alpha-synuclein expression in primary culture of rat CNS and in human erythroid leukemia cells. In mice, acute but not chronic dextran sulfate sodium-induced colitis was associated with a decreased expression of colonic alpha-synuclein. As a whole, our findings indicate that acute inflammatory insults down-regulate alpha-synuclein expression in the ENS via a p38 pathway. They provide new insights into the widely discussed concepts of alpha-synuclein expression and aggregation in the ENS in PD and raise issues about the possible role of gastrointestinal inflammation in the development of PD. OPEN SCIENCE BADGES: This article has received a badge for Open Materials because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
在帕金森病（PD）中强烈暗示表达的蛋白质α-突触核蛋白不仅在中枢神经系统（CNS）中表达，而且在肠神经系统（ENS）中表达。越来越多的证据表明，胃肠道炎症参与了 PD 的发展，这促使我们研究炎症对原代培养的大鼠 ENS 和葡聚糖硫酸钠诱导的结肠炎小鼠中α-突触核蛋白表达的影响。通过 Western blot 和 qPCR，我们发现脂多糖和肿瘤坏死因子-α与白细胞介素 1-β的组合均降低了原代培养大鼠 ENS 中α-突触核蛋白的表达水平，而 p38 抑制剂 SB203580 和 BIRB 796 的存在则阻止了这种作用。脂多糖和肿瘤坏死因子-α/白细胞介素 1-β对大鼠 CNS 原代培养物和人红白血病细胞中α-突触核蛋白的表达没有影响。在小鼠中，急性而非慢性葡聚糖硫酸钠诱导的结肠炎与结肠α-突触核蛋白表达降低有关。总的来说，我们的发现表明，急性炎症损伤通过 p38 途径下调 ENS 中的α-突触核蛋白表达。它们为广泛讨论的 PD 中 ENS 中α-突触核蛋白表达和聚集的概念提供了新的见解，并提出了胃肠道炎症在 PD 发展中的可能作用的问题。开放科学徽章：本文获得了开放材料徽章，因为它提供了重现手稿中研究所需的所有相关信息。本文的完整开放科学披露表格可以在文章末尾找到。有关开放实践徽章的更多信息，请访问 https://cos.io/our-services/open-science-badges/。
