Abnormalities in expression of RNA-binding proteins (RBPs) have been shown to be involved in the pathogenesis of a number of disorders, most notably amyotrophic lateral sclerosis. Recent data demonstrates these RBP abnormalities were also found in the brains of patients with multiple sclerosis (MS) and MS models. Oligodendrocyte-mediated myelination of neuronal axons is essential for axonal integrity and protects neurons from degeneration. Myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) are the two major components of central nervous system (CNS) myelin. The transport and translation of MBP and MAG mRNAs in oligodendrocytes are regulated by diverse RBPs. Our lab previously demonstrated that dysfunction of RBPs including heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in neurons is a key contributor to neurodegenerative-mediated mechanisms in MS and its models. Therefore, neurodegeneration is a component of MS pathology, however, the underlying mechanisms behind this remain unknown.
We tested the hypothesis that myelin-related RBPs are differentially expressed in the CNS of mice with experimental autoimmune encephalomyelitis (EAE).
EAE was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55). Animals (n=4 each EAE and naïve control) were observed clinically and spinal cord tissues were harvested at the peak of EAE for detection of the myelin related RBPs hnRNP A1, A2, K, E, and F using western blot.
Quantitative analyses showed a significant increase in hnRNP A1 protein expression (p=0.007, unpaired tailed t-test) in spinal cords of mice with EAE. In contrast, hnRNP A2 (p=0.03) and hnRNP K (p=0.002) showed reduced expression. There were no significant differences in the expression levels of hnRNP E and F comparing EAE with naïve animals.
These data indicate that altered expression of the myelin-related RBPs hnRNP A1, hnRNP A2, and hnRNP K may contribute to demyelination and neurodegeneration in EAE, which might also apply to the pathogenesis of MS.