A newly published study from Jenn Orthmann-Murphy’s group, a member of the White Matter Rounds community, sheds light on an important barrier to repair in multiple sclerosis: reactive microglia in the cortex.
In the article “Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination”, the authors investigate why the brain’s cortex struggles to remyelinate after injury. While much of Multiple Sclerosis (MS) research has focused on white matter, cortical demyelination is a critical contributor to progressive MS, and there are still no effective therapies to promote repair in this region.Using a mouse model of cortical demyelination, the team shows that after injury, microglia in the deep cortex become reactive, changing their shape and switching off homeostatic markers while increasing expression macrophages-associated markers. These changes persist during early recovery, exactly when new oligodendrocytes should be forming. Additionally, when the researchers temporarily depleted microglia during the recovery phase, oligodendrocyte regeneration improved. This suggests that reactive microglia in the deep cortex actively interfere with oligodendrocyte differentiation after demyelination.
These findings point to a promising therapeutic idea for progressive MS: targeting transiently reactive microglia at the right time and place could help unlock cortical remyelination and promote repair. The future implications of this study will extend beyond MS to other white matter diseases characterized by demyelination and microglia involvement.
