CX3CR1 knockout severely impacts cuprizone-induced demyelination. (A) Staining of myelin with Black Gold II was performed on brain sections from WT and CX3CR1^−/− mice 3 and 5 wk after the cuprizone treatment or normal chow. Representative photomicrographs are shown. (B) Quantification of demyelination was measured in the corpus callosum using a stereological procedure 5 wk after normal chow or cuprizone treatment in WT and CX3CR1^−/− mice. (C) Time spent in the open arm of the elevated plus maze behavioral test, efficient to assess behavioral deficits induced by cuprizone (Lister, 1987). (D) Stereologic assessment of APC⁺ cells in the corpus callosum of WT and CX3CR1^−/− mice after 5 wk of a cuprizone-supplemented diet or normal chow. APC is a specific marker for mature myelinating oligodendrocytes. (E) Representative electron microscopy images of oligodendrocytes in the corpus callosum of CX3CR1^−/− mice, either untreated, or after 6 wk of a cuprizone-supplemented diet. One representative experiment out of two is shown. n = 4–12 mice/group. (B) **, P = 0.002; ****, P < 0.0001; (C and D) **, P = 0.0093; ****, P < 0.0001. Bars: (A) 100 µm; (E) 2 µm.