Corpus callosum is affected later than other brain regions. (A-B) Microglia (F4/80, green), axonal swellings (APP, red) or damage (SMI32, red) and myelin (MBP, blue) were co-labeled on sagittal brain section. At six weeks no pathology was observed yet in the corpus callosum, but at 12 weeks demyelination was pronounced and associated with microgliosis (B) and axonal swellings (Inset in B, arrow). (C-D) Healthy axons were massively lost at 12 weeks, as shown by decreased SMI31 immunoreactivity (D), compared to control mice (C). (E-F) Potassium channels (K+) were immunolabeled to visualize the juxtaparanodes. In the 12-week-old Nestin-Pex5
−/− mice these juxtaparanodes displayed a broader distribution (F, arrow), in comparison with the control mice (E). (G-H) Astrocytes were labeled with anti-GFAP. Astrogliosis is strongly pronounced at 12 weeks (H), in comparison with the control mouse (G). Scale bars: A-D: 100 μm; G-H: 10 μm; Inset in B: 12 μm. APP: amyloid precursor protein, GFAP: glial fibrillary acidic protein, K+: potassium, MBP: myelin basic protein, SMI: Sternberger monoclonals Inc.