当前位置: X-MOL 学术J. Inflammation Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates.
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2019-05-07 , DOI: 10.2147/jir.s196552
Henry Resnikoff 1 , Jeanette M Metzger 1, 2 , Mary Lopez 1 , Viktoriya Bondarenko 1 , Andres Mejia 1 , Heather A Simmons 1 , Marina E Emborg 1, 2, 3
Affiliation  

Background: Parkinson’s disease (PD) patients frequently present gastrointestinal (GI) dysfunction that, in many cases, predates the onset of motor symptoms. In PD, the presynaptic protein alpha-synuclein (α-syn) undergoes pathological changes, including phosphorylation and aggregation leading to the formation of Lewy bodies, which can be found in neurons of the enteric nervous system (ENS). Inflammation has been proposed as a possible trigger of α-syn pathology. Interestingly, patients with inflammatory bowel disease and irritable bowel syndrome, conditions associated with GI inflammation, are at higher risk of developing PD. Captive common marmosets (Callithrix jacchus) develop colitis, providing a natural platform to assess the relationship between α-syn pathology and GI inflammation.
Materials and Methods: Sections of proximal colon from marmosets with colitis (n=5; 5.3±2.3 years old; 4 male) and normal controls (n=5; 4.1±1.6 years old; 1 male) were immunostained against protein gene product 9.5 (PGP9.5), human leukocyte antigen DR (HLA-DR), cluster of differentiation 3 (CD3), cluster of differentiation 20 (CD20), glial fibrillary acidic protein (GFAP), 8-hydroxy-2’-deoxyguanosine (8-OHdG), α-syn, and serine 129 phosphorylated α-syn (p-α-syn). Immunoreactivity of each staining in the myenteric plexus was quantified using NIH ImageJ software.
Results: Marmosets with colitis had significantly increased expression of inflammatory markers (HLA-DR, p<0.02; CD3, p<0.008), oxidative stress (8-OHdG, p<0.05), and p-α-syn (p<0.02) and decreased expression of α-syn (p<0.04) in the colonic myenteric ganglia compared to normal, healthy controls.
Conclusion: Colonic inflammation is associated with changes in α-syn expression and phosphorylation in the myenteric plexus of common marmosets. Future evaluation of the vagus nerve and brain of animals with colitis will be key to assess the contribution of colitis-induced ENS α-syn pathology to PD-like pathology in the brain.



中文翻译:

结肠炎症会影响非人类灵长类动物的肠系膜α-突触核蛋白。

背景:帕金森氏病(PD)患者经常出现胃肠道(GI)功能障碍,在许多情况下,这是运动症状发作之前的。在PD中,突触前蛋白α-突触核蛋白(α-syn)发生病理变化,包括磷酸化和聚集,导致形成路易小体,这可在肠道神经系统(ENS)的神经元中发现。有人提出炎症可能是α-syn病理的触发因素。有趣的是,患有炎症性肠病和肠易激综合症(与胃肠道炎症相关的疾病)的患PD的风险更高。圈养普通mar(Callithrix jacchus)会发展为结肠炎,为评估α-syn病理学与GI炎症之间的关系提供了自然的平台。
材料与方法:对患有结肠炎的mar猴(n = 5; 5.3±2.3岁; 4名男性)和正常对照组(n = 5; 4.1±1.6岁; 1名男性)的近端结肠部分进行蛋白蛋白产物9.5免疫染色。 (PGP9.5),人白细胞抗原DR(HLA-DR),分化簇3(CD3),分化簇20(CD20),神经胶质纤维酸性蛋白(GFAP),8-羟基-2'-脱氧鸟苷(8 -OHdG),α-syn和丝氨酸129磷酸化的α-syn(p-α-syn)。使用NIH ImageJ软件定量分析肌间神经丛中每种染色的免疫反应性。
结果:患有结肠炎的Mar猴的炎症标志物(HLA-DR,p <0.02; CD3,p <0.008),氧化应激(8-OHdG,p与正常,健康的对照组相比,结肠肌层神经节中的p-α-syn(p <0.02)和p-α-syn(p <0.02)降低,α-syn的表达降低(p <0.04)。
结论:结肠炎与普通mar猴的肌间神经丛中α-syn表达和磷酸化的改变有关。结肠炎动物的迷走神经和大脑的未来评估将是评估结肠炎诱发的ENSα-syn病理学对大脑PD样病理学的贡献的关键。

更新日期:2019-05-07
down
wechat
bug