Brain lipid binding protein expression in remyelinating Schwann cells of the spinal cord in multiple sclerosis

Myelin is important for axon maintenance and survival, as well as for saltatory conduction of nerve impulses. Consequently, loss of myelin after spinal cord injury or in demyelinating diseases such as Multiple Sclerosis (MS) results in dysfunction of nerve impulse propagation and progressive axonal damage and cell death. Endogenous remyelination can occur in response to MS and is mainly mediated by oligodendrocyte precursor cell-derived oligodendrocytes, but Schwann cells (SCs) can also participate. SC remyelination has been documented in spinal cord lesions following traumatic spinal cord injury in humans, and in animal models of demyelination such as lysolecithin-induced demyelination, but endogenous remyelination by SCs in the context of MS has not been as well studied. In the present study we used immuno-fluorescent detection to analyze the expression of brain lipid binding protein (BLBP) and peripheral myelin protein zero (P0) in MS and non-MS human spinal cord as well as in the lysolecithin-demyelinated mouse spinal cord. BLBP (also known as Fatty Acid Binding Protein 7) is a nervous system-specific fatty acid binding protein. In the context of the present study, BLBP is important because it has been previously used to identify spinal cord radial glia (RG) in the developing and adult mouse spinal cord. BLBP is also expressed by SC precursors, and by immature SCs before they differentiate into myelinating SCs. We investigated whether, like the mouse spinal cord, the aged human spinal cord preserves a population of BLBP+ spinal cord RG. We found that (1) in contrast to the mouse spinal cord RG, human spinal cord RG do not express BLBP; (2) unlike the mouse, some subpopulations human myelinating SCs express BLBP in the PNS of MS (and some non-MS) cases; (3) in the MS spinal cord, BLBP-positive SCs extensively myelinate axons in large GFAP-rich areas; (4) and that BLBP is more readily detected in uncompacted myelin sheaths. Collectively these data provide evidence of robust SC remyelination in the human spinal cord beyond what has been previously reported, and highlight BLBP as a developmentally regulated protein whose expression is significantly different between mouse and human spinal cord RG and SCsMedicine, Faculty ofGraduat