Neuromyelitis Optica (NMO) is a rare auto-immune demyelinating disease related to multiple sclerosis. Patients present autoantibodies (called NMO-IgG) targeting aquaporin-4 (AQP4), the main water channel of the brain mostly expressed at the perivascular processes of astrocytes. The link between astrocyte targeting by NMO-IgG and demyelination is now well established. However another type of cells express also AQP4 in the brain: ependymocytes. Ependyma lines all the cavities of the central nervous system filled with cerebrospinal fluid. These cells regulate import brain functions (e.g., cerebrospinal fluid circulation, molecular homeostasis, subventricular stem cell niche) and clinical evidences suggest ependyma is targeted in NMO.
The objective of my PhD is to evaluate the effects of NMO-IgG purified from patients' sera on different models of ependyma. I use primary cultures from newborn rats, cultured explants of rat lateral ventricles and a home-made rat model of NMO based on the chronic infusion of NMO-IgG directly in the ventricles via an osmotic pump. Ependymal functions are then assessed with immunolabeling, RNA sequencing and ependymal flow analysis.
