Fig. 4.
Age-dependent progression in PNS macrophage activation is accompanied by significant deposition of antibodies and complement. (A) Representative sciatic nerves from mSOD1G93A mice were stained for CD68/Iba1+ macrophages. At week 5, endoneural macrophages are morphologically un-activated. At weeks 9 and 11, macrophages accumulate in nerves, becoming activated morphologically, often assembling in rows. At weeks 14 to 19, activated macrophages spread throughout nerve parenchyma. (Scale bars: 100 μm.) (B) Quantification of progressive macrophage activation in sciatic nerves of mSOD1G93A and non-Tg mice (20× fields of non-consecutive 14 μm sections analyzed; mean ± SEM, ***, P < 0.001). (C) Week 19 mSOD1G93A, week 19 non-Tg, and 6-month-old mSOD1G37R sciatic nerve sections were stained for complement C3 (green) and antibody IgM (red). Strong deposition of complement and antibodies was observed in ALS Tg nerves. (D) Separate week-19 sections show anti-IgG reactivity in mSOD1G93A but not non-Tg nerves. (E) At presymptomatic weeks 9 and 10, antibody IgM (red) co-localizes in PNS tissue with strands of activated macrophages (CD68, green).