Recurrent systemic infections with Streptococcus pneumoniae do not aggravate the course of experimental neurodegenerative diseases.
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.
Ebert
Sandra
S
Department of Neurology, University of Göttingen, Göttingen, Germany. sebert1@gwdg.de
Goos
Miriam
M
Rollwagen
Lena
L
Baake
Daniel
D
Zech
Wolf-Dieter
WD
Esselmann
Hermann
H
Wiltfang
Jens
J
Mollenhauer
Brit
B
Schliebs
Reinhard
R
Gerber
Joachim
J
Nau
Roland
R
D000208:Acute Disease; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D015850:Interleukin-6 / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000150:complications* / Q000276:immunology*; D012008:Recurrence; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D051844:alpha-Synuclein / Q000235:genetics
D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D051844:alpha-Synuclein; D002443:Ceftriaxone