5-HT2a receptor pathway in oligodendrocyte differentiation: its involvement in Multiple Sclerosis pathogenesis

Multiple sclerosis (MS) is a chronic demyelinating disease affecting the neurons of brain and spinal cord. In chronic MS lesions oligodendrocytes (the myelin synthesizing cells) precursor cells (OPCs) accumulate with loss of mature OLs, suggesting a differentiation block of OPCs. In MS patients during the active phase of the disease (poussà¨) the disruption of the blood brain barrier can allow serum antibodies and other molecules to reach the CNS, producing demyelination. Here we demonstrate that IgGs, isolated from MS patients during the acute phase, inhibit PMA-induced differentiation of OPCs by reducing the expression of the OLs differentiation markers in the human OL cell line, MO3-13. In a more specific setting, we found that IgGs from MS patients inhibit differentiation driven by P-ERK activation, The identification of a putative receptor targeted by IgGs present in the biological fluids of MS patients will pave the way to dissect the ERK1/2-dependent signalling pathway leading to demyelination in MS.