Department of Neurology, University of Göttingen, Göttingen, Germany.
J Neurosci Res. 2010 Apr;88(5):1124-36. doi: 10.1002/jnr.22270.
Neurological symptoms of patients suffering from neurodegenerative diseases such as Alzheimer's dementia (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) often worsen during infections. We assessed the disease-modulating effects of recurrent systemic infections with the most frequent respiratory pathogen, Streptococcus pneumoniae, on the course of AD, PD, and ALS in mouse models of these neurodegenerative diseases [transgenic Tg2576 mice, (Thy1)-[A30P]alpha SYN mice, and Tg(SOD1-G93A) mice]. Mice were repeatedly challenged intraperitoneally with live S. pneumoniae type 3 and treated with ceftriaxone for 3 days. Infection caused an increase of interleukin-6 concentrations in brain homogenates. The clinical status of (Thy1)-[A30P]alpha SYN mice and Tg(SOD1-G93A) mice was monitored by repeated assessment with a clinical score. Motor performance was controlled by the tightrope test and the rotarod test. In Tg2576 mice, spatial memory and learning deficits were assessed in the Morris water maze. In none of the three mouse models onset or course of the disease as evaluated by the clinical tests was affected by the recurrent systemic infections performed. Levels of alpha-synuclein in brains of (Thy1)-[A30P]alpha SYN mice did not differ between infected animals and control animals. Plaque sizes and concentrations of A beta 1-40 and A beta 1-42 were not significantly different in brains of infected and uninfected Tg2576 mice. In conclusion, onset and course of disease in mouse models of three common neurodegenerative disorders were not influenced by repeated systemic infections with S. pneumoniae, indicating that the effect of moderately severe acute infections on the course of neurodegenerative diseases may be less pronounced than suspected.
患有神经退行性疾病（如阿尔茨海默病痴呆症（AD）、帕金森病（PD）或肌萎缩侧索硬化症（ALS））的患者的神经症状在感染期间往往会恶化。我们评估了反复发生的全身性感染最常见的呼吸道病原体肺炎链球菌（Streptococcus pneumoniae）对这些神经退行性疾病的小鼠模型（Tg2576 转基因小鼠、（Thy1）-[A30P]alpha SYN 小鼠和 Tg（SOD1-G93A）小鼠）中 AD、PD 和 ALS 病程的调节作用。小鼠通过腹膜内重复挑战活 S. pneumoniae 3 型并用头孢曲松治疗 3 天。感染导致脑匀浆中白细胞介素-6 浓度增加。（Thy1）-[A30P]alpha SYN 小鼠和 Tg（SOD1-G93A）小鼠的临床状态通过临床评分的重复评估进行监测。运动性能通过绳索测试和旋转杆测试进行控制。在 Tg2576 小鼠中，通过 Morris 水迷宫评估空间记忆和学习缺陷。在三种小鼠模型中，通过临床测试评估的疾病发作或病程均不受反复进行的全身性感染的影响。感染动物和对照动物的（Thy1）-[A30P]alpha SYN 小鼠脑中的 alpha-synuclein 水平没有差异。感染和未感染的 Tg2576 小鼠脑中的斑块大小和 A beta 1-40 和 A beta 1-42 的浓度没有显著差异。总之，三种常见神经退行性疾病小鼠模型的疾病发作和病程不受肺炎链球菌反复全身性感染的影响，这表明中度严重急性感染对神经退行性疾病病程的影响可能不如预期的那么明显。
