Accelerated axon loss in MOG35-55 experimental autoimmune encephalomyelitis (EAE) in myelin-associated glycoprotein-deficient (MAGKO) mice

Abstract Myelin-associated glycoprotein (MAG) expressed by oligodendrocytes promotes the stability of axons but also impedes neural repair by inhibiting axon extension through lesioned white matter. We previously reported exacerbated axon losses in MAGKO as compared to wild type mice, 30 days into experimental autoimmune encephalitis (EAE). Here, we report the time course of axon losses in EAE and show this occurs as early as 7 days post-immunization, confirming MAG is protective against immune-mediated axon transection events. MAGKO mice also exhibit increased microglial activation prior to EAE, which is not seen in B4galnt1KO mice that also have axon loss, suggesting that the microglial activation may be a consequence of the loss of MAG inhibitory influence, and not a simple result of axonal degeneration.