Figure 4.

Microglia upregulate Axl and Mer in response to cuprizone challenge. a–f, Double-immunoperoxidase staining for Axl and Mer (brown) and IBA1 (blue) in the midline corpus callosum of unchallenged mice or mice challenged with cuprizone for 2 or 4 weeks (n = 4 for each time point). a, b, In unchallenged animals, a small number of IBA1-positive cells, evenly distributed throughout the corpus callosum, was observed. At this time point, cells positive for either Axl (a) or Mer (b) were rarely observed. c, d, After 2 weeks of cuprizone challenge, a small increase in the number of IBA1-positive cells was observed. k, l, Some of the IBA1-positive cells were also positive for Axl (k) or Mer (l). Cells positive for Axl or Mer alone were rarely observed. e, f, After 4 weeks of cuprizone challenge, the number of IBA1-positive cells in the corpus callosum was greatly increased, with a concomitant increase in Axl (e) and Mer (f) immunoreactivity among IBA1-positive cells, although Mer reactivity appeared less extensive. g, h, The dissociation between Axl- and Mer-positive cells is shown in staining of adjacent sections from mice challenged with cuprizone for 4 weeks. g–j, Axl positivity (g, i) appears to extend throughout the region of IBA1 expression, whereas Mer appears restricted to a subset of IBA1-positive microglia (h, j). Scale bars: a–f, i, j, 100 μm; g, h, 200 μm; k, l, 50 μm.