Knockout of sialoadhesin enhances microglial accumulation during prion pathogenesis

Introduction: The adhesion molecule sialoadhesin binds sialic acid residues of glycoproteins and promotes endocytosis. To determine if sialoadhesin played a role in the uptake and pathogenesis of prion infectious-agent, scrapie challenge studies were performed in sialoadhesin–deficient (SnKO) transgenic mice.
Methods: Groups of SnKO mice and C57Bl/6 (wt) control mice were inoculated intracerebrally or intraperitoneally with mouse adapted scrapie agent ME7. Mice were studied at 5, 10 and 15 weeks for peripheral prion pathogenesis following i.p. inoculation.
Results: Following intraperitoneal infection SnKO mice revealed no significant differences to wt mice in all aspects studied, including assessment of immune function via antigen trapping assays and disease-associated PrP accumulation in lymphoid follicles. Following intracerebral infection alterations were observed in brain region-specific microglial responses resulting in elevated levels of disease-associated vacuolation in hippocampal CA1 region and enhanced microglial accumulation, verified by morphometric analysis.
Conclusions: In SnKO mice the lack of sialoadhesin on microglia enhanced their response to infection following disruption of the blood brain barrier. These data also suggest that prion-induced vacuolation can be modulated by microglial response and that response may be primed at the initial stage of infection.