Figure 1

Minocycline corrects neuroinflammation in young, pre-plaque Tg mice. (A-C) Representative western blots for iNOS, COX-2 and IL-1β (typical markers of microglial and neuronal activation) in control, Non Tg Placebo mice (Non Tg), Tg Placebo mice (Tg Pl) and Tg mice treated with minocycline (Tg Mino). Note the significant up-regulation of iNOS and COX-2 in Tg Pl compared to Non Tg. Minocycline restored iNOS and COX-2 to levels similar to those of Non Tg, and significantly reduced the levels of IL-1β (* P < 0.05, **P < 0.01, one-way ANOVA with Tukey post-hoc test). See main text for the values of Non Tg treated with minocycline. (D) Schematic illustrating the sampling of images in the CA1 area of the hippocampus and from the lateral posterior thalamic nucleus as utilized for the morphological study represented in E-G. (E) Representative micrographs illustrating the ir of Iba-1 in microglial cells in the hippocampus of the Non Tg, Tg Pl and Tg Mino mice. Note the altered morphology of the microglial cells in Tg Pl compared to Non Tg. In Tg Pl mice, we observed an enlargement of the soma size, polarization and thickening of the microglial processes, which are classical indicators of microglial activation. Minocycline treatment resulted in correction of microglial soma size (note the small, roundish morphology), with some residual thickening of processes and increase in spiny processes. (F) Representative micrographs illustrating the ir of Iba-1 in microglial cells in the lateral posterior thalamic nucleus of the Non Tg, Tg Pl and Tg Mino. The cells were notably smaller and less ramified than in the hippocampus, but no differences in the morphology could be observed between experimental groups. Scale bar for E and F: 20 μm. (G,H) Quantification of cell soma size and density of microglial cells from hippocampus (G) and thalamus (H) in Non Tg, Tg Pl and Tg Mino. Note that minocycline treatment resulted in significant reduction of microglial cells soma size compared to Tg Pl in the hippocampus (G). No significant differences were observed in the soma size of cells in the thalamus (H). As previously reported [23], no significant changes in microglial cell density were observed between Non Tg and Tg. This pattern was not altered across experimental groups in any area. (* P < 0.05, one-way ANOVA followed by Tukey post-hoc test). Non Tg: Non Tg Placebo mice; Tg Mino: Tg mice treated with minocycline; Tg Pl: Tg Placebo.