title: Viral-induced inflammation is accompanied by beta-amyloid plaque reduction in brains of amyloid precursor protein transgenic Tg2576 mice.
abstract: Amyloid plaques, one of the neuropathological hallmarks of Alzheimer's disease, and their main constituent, the amyloid beta-peptide (Abeta), are triggers of the activation of innate inflammatory mechanisms involving the activation of microglia. To dissect the effects of a non-Abeta-specific microglial activation on the Abeta metabolism, we employed a viral infection-based model. Transgenic mice expressing a mutated form of the human amyloid precursor protein (Tg2576) were used. In preceding experiments, 2-week-old transgenic mice and non-transgenic littermates were infected intracerebrally with the neurotropic Borna disease virus and investigated at 2, 4 and 14 weeks post-infection. The Borna disease virus-inoculated mice showed a persisting, subclinical infection of cortical and limbic brain areas characterized by slight T-cell infiltrates, expression of cytokines and a massive microglial activation in the hippocampus and neocortex. Viral-induced effects reached their peak at 4 weeks post-infection. In 14-month-old Tg2576 mice, characterized by the deposition of diffuse and dense-core amyloid plaques in cortical brain regions, Borna disease virus-induced microglial activation in the vicinity of Abeta deposits was used to investigate the influence of a local inflammatory response on these deposits. At 4 weeks post-infection, histometric analyses employing Abeta immunohistochemistry revealed a decrease of the cortical and hippocampal Abeta-immunopositive area. This overall decrease was accompanied by a decrease of parenchymal thioflavin-S-positive amyloid deposits and an increase of such deposits in the walls of cerebral vessels, which indicates that the elicitation of a non-Abeta-specific microglial activation may contribute to a reduction of Abeta in the brain parenchyma.
authors.affiliation: Department of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 43, D-04109 Leipzig, Germany. stahl@vmf.uni-leipzig.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Stahl
authors.forename: Christine
authors.initials: C
authors.lastname: Reimers
authors.forename: Reimar
authors.initials: R
authors.lastname: Johne
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schliebs
authors.forename: Johannes
authors.initials: J
authors.lastname: Seeger
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D052160:Benzothiazoles; D001891:Borna disease virus; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009698:Nucleoproteins / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013844:Thiazoles; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009698:Nucleoproteins; D013844:Thiazoles; D014764:Viral Proteins; C009462:thioflavin T