Einfluss einer intrazerebralen Infektion mit Escherichia coli auf den Verlauf der Alzheimer-Demenz im Mausmodell

Abstract

Bacterial infections often worsen the existing neurological symptoms of patients with neurodegenerative diseases such as Alzheimer´s disease. Not only the acute consequences in the sense of a delirium but also the long-term consequences of bacterial infections could be shown in clinical studies. In the present work, these clinical observations could also be shown in an animal experiment. For the first time it was possible to cause a long-term worsening of a neurodegenerative disease by a real infection. Transgenic mice of the strain Tg2576, which overexpress the Aβ-Precursor-Protein, as well as non-transgenic mice at the age of 10 to 15 months were intracerebrally infected with Escherichia coli K1. Non-infected control mice were intracerebrally injected with a 0,9% sodium chloride solution. After 41 hours all laboratory animals were treated with the bactericidal antibiotic ceftriaxone for five days. The cognitive functions of the mice were examined using the Morris Water Maze neuropsychological test procedure. No differences were found between infected and non-infected mice concerning their memory functions within 4 weeks after infection. However, infected transgenic mice showed a significant impairment concerning their learning ability. Four weeks after an intracerebral infection the infected transgenic mice were not able to learn the new localisation of a platform in the Morris Water Maze. In contrast, non-infected mice were able to learn the new localisation of the platform as fast as before the infection. Motor performances which were examined by the tight rope test and the Rotarod test did not differ between infected and non-infected mice. These observations suggest that infections not only have an acute negative impact on neurodegenerative diseases but also lead to a progression of the disease symptoms in the long run. This progression of the disease could be demonstrated particularly for female mice which showed a stronger cognitive impairment after an intracerebral bacterial infection than male mice. Brains of the mice were examined by use of ELISA with respect to the concentrations of β-amyloids (Aβ) 1-40 and 1-42 and, additionally, with respect to the size of the β-amyloid-plaques by use of thioflavin-s-staining. Both examinations did not show any differences between infected and non-infected mice. The results of the present work indicate that an adequate, quick and aggressive antibiotic treatment of a bacterial infection could be particularly advantageous for patients with neurodegenerative diseases. Furthermore, the choice of an antibiotic which does not disrupt the cell wall synthesis and leads to a lower release of bacterial compounds might reduce the negative impact of bacterial infections on the course of neurodegenerative diseases.