Walsh Sinéad, Gavin Aisling, Wyatt Séan, O'Connor Catriona, Keeshan Karen, Nolan Yvonne M, O'Keeffe Gerard W, Sullivan Aideen M
1Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork , Cork , Ireland.
Int J Neurosci. 2015 Jan;125(1):70-7. doi: 10.3109/00207454.2014.904304. Epub 2014 Apr 14.
It is well established that neuroinflammation is associated with the progression of many neurodegenerative diseases, including Parkinson's disease (PD). Activated microglia and elevated levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) have been found in the brain and cerebrospinal fluid of PD patients, suggesting that IL-1β may be involved in the pathogenesis of this disease. This study aimed to knock down the expression of the interleukin-1 type 1 receptor (IL-1R1) to evaluate any potential therapeutic effect of limiting the action of IL-1β in the substantia nigra following a unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion in rats. Adult Sprague-Dawley rats received intranigral injections of shRNA specific for IL-1R1, followed 2 weeks later by intrastriatal 6-OHDA. Injection of IL-1R1 shRNA did not prevent 6-OHDA-induced loss of motor function or loss of nigral dopamine neurons. IL-1R1 expression was increased in the midbrain following 6-OHDA injection; this effect was attenuated in 6-OHDA-treated animals that had received IL-1R1 shRNA. These data suggest that while IL-1R1 was increased in 6-OHDA-treated animals and reduced following shRNA injection, the neurodegeneration induced by 6-OHDA was not mediated through IL-1R1.
众所周知，神经炎症与包括帕金森病（PD）在内的许多神经退行性疾病的进展相关。在PD患者的大脑和脑脊液中发现了活化的小胶质细胞以及促炎细胞因子如白细胞介素-1β（IL-1β）水平升高，这表明IL-1β可能参与了该疾病的发病机制。本研究旨在敲低白细胞介素-1Ⅰ型受体（IL-1R1）的表达，以评估在大鼠单侧纹状体内注射6-羟基多巴胺（6-OHDA）损伤后，限制IL-1β在黑质中的作用的任何潜在治疗效果。成年Sprague-Dawley大鼠接受针对IL-1R1的shRNA黑质内注射，2周后进行纹状体内6-OHDA注射。注射IL-1R1 shRNA并不能预防6-OHDA诱导的运动功能丧失或黑质多巴胺能神经元丧失。6-OHDA注射后中脑内IL-1R1表达增加；在接受IL-1R1 shRNA的6-OHDA处理动物中，这种效应减弱。这些数据表明，虽然在6-OHDA处理的动物中IL-1R1增加，且在注射shRNA后降低，但6-OHDA诱导的神经退行性变并非通过IL-1R1介导。
