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

Abstract

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.

Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis

“…In accordance with our observations, the disease-aggravating effect of LPS observed in other neurodegenerative disease models [31, 32] could also not be confirmed in mouse models of Alzheimer’s and Parkinson’s disease when real systemic infections were induced by viable S. pneumoniae [31, 33] or E. coli (Schütze et al, unpublished observation).…”

Follistatin Does Not Influence the Course of Escherichia coli K1 Sepsis in a Mouse Model

“…Mice that hung 60 s on the rope but did not reach one of the platforms were given a score of 10. If a mouse fell off the rope before 60 s, an additional point was added to the 10 points for every 6 s it fell before the 60-s point (24,25).…”

Systemic inflammation and delirium: important co-factors in the progression of dementia

“…Using another model of Parkinson’s disease, induced by intra-nigral injection of LPS, Villaran et al showed that ulcerative colitis could also significantly exacerbate dopaminergic neuronal loss (28). Interestingly, infection with the Gram-positive bacterium Streptococcus pneumoniae did not exacerbate features of disease in a number of disease models (54). Although these studies are confounded to some degree by the administration of antibiotics to all infected animals within 24 hours of infection it may be of interest that Gram-positive bacteria, lacking LPS, may constitute a less significant insult to the diseased brain.…”