Figure 14

Assessment of CD45, CD11b and CD206 microglial activation states 12 hrs post CpG ODN injection. An acute injection of CpG ODN led to an induction of favorable microglia/macrophage activation in 3xTg-AD mice. Immunohistochemistry indicated a significant increase in CD45 (young, **p = 0.001; aged, *p = 0.01) ( A , B ), CD11b (young, **p = 0.0013; aged, *p = 0.02) ( D , E ) and CD206 (young, *p = 0.017; aged, **p = 0.006) ( G , H ) macrophage/microglia markers 12 hrs after CpG ODN administration in both age cohorts of 3xTg-AD mice. The assessment of microglial cell activation after a single i.p. injection of either CpG ODN or saline was based on semiquantitative analysis of the extent of microgliosis in the hippocampus ( C , F , I ). Scale bars, 100 µm. CD45 and CD206 positive cells, likely to be infiltrating peripheral macrophages, were clearly restricted to AD pathology. Co-staining of microglial markers (CD45 or CD206, green) and Aβ deposits (6E10/4G8, red) revealed an increase in CD45 and CD206 immunoreactive microglia around the plaques in mice injected with CpG ODN, 12 hrs post CpG ODN injection. Confocal microscopy confirmed partial co-localization of CD45 and CD206 positive microglia with 6E10/4G8 positive Aβ deposits ( J , K ). Arrows indicate co-localization. In addition, double immunofluorescence for microglial markers (CD45 or CD206, green) and pathological tau (MC1, red) indicated an increase in CD45 and CD206 microglial activation in association with MC1 reactive pathological tau within hippocampal neuronal perikarya and neuronal processes, as well as dystrophic neurites ( L , M ). J - M show representative hippocampal images from 20 month old Tg-control and Tg-CpG ODN mice. Similar increase in activation of CD45 and CD206 microglial cells in the vicinity of AD pathology was observed in 12 month old CpG ODN-injected animals (data not shown). Scale bars, 50 µm.