Fig. 1From: ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activationNeuronal upregulation of ISG15 in vivo in demyelinating disease models. ISG15 expression in Syn.Cre-Rpl22 “ribotag” mouse cortex (A) or B6 retina (B) during EAE (Day 18) or cuprizone (6 weeks) induced demyelination compared to controls. Mean ± SEM are shown. C Coronal sections were stained for ISG15 and markers of neuronal dendrites (MAP2) and axons (NFL) as well as glial markers. ISG15 primarily localized to neuronal soma and dendrites. D ISG15 immunoblot in cerebral cortex, spinal cord, and brain stem of EAE and cuprizone mice compared to controls showing typical smear pattern indicative of ISGylated targets. E Thick-cut vibratome sagittal sections from B6 mice on cuprizone diet, at peak EAE, or controls were immunostained for ISG15 and counterstained with DAPI. Representative confocal images of cortex, cerebellum, and brain stem are shown. F Similar ISG15 staining in hippocampus for B6 and IFNAR KO mice on cuprizone diet, at peak EAE, or controls is shown. Scale bars 50 microns. G ISG15 immunoblot in spinal cord of non-symptomatic EAE mice (EAE-NS) and symptomatic EAE mice (EAE-S) compared to controls as in D for B6 and IFNAR KO mice. **P < 0.05Back to article page