Genetically controlled preferential loss of myelin-associated glycoprotein (MAG) coincides with severity and relapsing course of experimental autoimmune encephalomyelitis in H-2b/s mice (B85)

Abstract Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are demyelinating diseases of central nervous system (CNS). Four types of demyelinating lesions and associated distinct immunopathogenetic mechanisms reflect heterogeneity of clinical MS. It is unknown if demyelinating patterns in EAE recapitulate those found in MS. We investigated patterns of demyelination in genetically related H-2band H-2b/s mice following immunization with H-2b restricted immunodominant epitope of myelin oligodendrocyte protein (MOG35–55). We measured loss of myelin proteins specifically, MOG, myelin associated glycoprotein (MAG), myelin basic protein (MBP), and levels of neurofilament (NF160), and DNA-binding apoptosis regulatory protein (PARPp80) in demyelinating lesions of EAE mice. While loss of MOG was apparent in both strains during acute disease, it was significantly higher in H-2b/s compared to H-2b mice. Conversely, profound depletion of MAG, accompanied with decreased NF160, and elevated PARPp80 levels were exclusively found in severely relapsing H-2b/s mice. Levels of MBP remained relatively unchanged in both strains. Our data show that preferential loss of MAG, which is suggestive of distal oligodendrogliopathy, associates with reduction of axonal neurofilament, signs of apoptosis, and severe relapsing disease in H-2b/s mice. We propose that pattern of demyelination in H-2b/s mice resembles the type III MS lesion.