Figure 9From: Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system Cerebellar and cortical dysmyelination in Gnpat −/− mice in the absence of microglia activation. (A-L) Immunohistochemistry was performed to investigate myelin (MBP), axonal loss (SMI31), microgliosis (F4/80) and oxidative stress (4-HNE and 3-nitrotyrosine). Gnpat −/− mice displayed a decreased amount of myelin in the cerebellar folia at three months (B), compared with the control littermates (A). Cortical demyelination was observed in a subset of three-month-old Gnpat knockout mice (G-H). Axonal loss was very mild at three weeks (C-D) and five months (E-F) and also a few axonal swellings were detectable with SMI31 (red) at five months (F, arrow and inset). Microgliosis (F4/80, green) was absent (F). 3-Nitrotyrosine (3-NT) and 4-HNE positive Purkinje cells were seen in three-week-old Gnpat −/− mice (J, L), in comparison with the control mice (I, K). Scale bars: A-F and I-L: 100 μm; G-H: 50 μm. (M) Quantification of mRNA levels of the pro-inflammatory markers TNFα, TLR2 and C1q by qRT-PCR. Expression levels were not elevated in four- to five-month-old Gnpat knockout mice. Values represent means ± SEM of four independent samples. Expression levels were normalized to β-actin expression. 4-HNE, 4-hydroxynonenal; TLR2, toll-like receptor 2; SEM, standard error of the mean.Back to article page