Recurrent systemic infections with Streptococcus pneumoniae do not aggravate the course of experimental neurodegenerative diseases

• Published in: Journal of neuroscience research Vol. 88; no. 5; pp. 1124 - 1136
• Main Authors: Ebert, Sandra, Goos, Miriam, Rollwagen, Lena, Baake, Daniel, Zech, Wolf-Dieter, Esselmann, Hermann, Wiltfang, Jens, Mollenhauer, Brit, Schliebs, Reinhard, Gerber, Joachim, Nau, Roland
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2010
• Subjects: Acute Disease; alpha-Synuclein - genetics; Alzheimer Disease - genetics; Alzheimer Disease - immunology; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - immunology; Amyotrophic Lateral Sclerosis - physiopathology; Animals; Anti-Bacterial Agents - pharmacology; Ceftriaxone - pharmacology; Disease Models, Animal; Disease Progression; Interleukin-6 - metabolism; Maze Learning - physiology; Memory Disorders - genetics; Memory Disorders - immunology; Memory Disorders - physiopathology; Mice; Mice, Transgenic; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - physiopathology; Neuropsychological Tests; Parkinson Disease - genetics; Parkinson Disease - immunology; Parkinson Disease - physiopathology; Parkinson's disease; Plaque, Amyloid - genetics; Plaque, Amyloid - immunology; Plaque, Amyloid - metabolism; Pneumonia, Bacterial - complications; Pneumonia, Bacterial - immunology; Recurrence; Streptococcal Infections - complications; Streptococcal Infections - immunology; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology; systemic infection; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0360-4012; 1097-4547; 1097-4547
• 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]αSYN 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]αSYN 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 α‐synuclein in brains of (Thy1)‐[A30P]αSYN mice did not differ between infected animals and control animals. Plaque sizes and concentrations of Aβ 1–40 and Aβ 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. © 2009 Wiley‐Liss, Inc.