Galectin-4, a Negative Regulator of Oligodendrocyte Differentiation, Is Persistently Present in Axons and Microglia/Macrophages in Multiple Sclerosis Lesionsde Jong, C. G. H. M., Stancic, M., Pinxterhuis, T. H., van Horssen, J., van Dam, A-M., Gabius, H-J. & Baron, W., Nov-2018, In : Journal of neuropathology and experimental neurology. 77, 11, p. 1024-1038 15 p.
Research output: Contribution to journal › Article › Academic › peer-review
Neuron-derived molecules are potent regulators of oligodendrocyte differentiation and myelination during brain development and upon demyelination. Their analysis will thus contribute to understanding remyelination failure in demyelinating diseases, such as multiple sclerosis (MS). Previously, we have identified neuronal galectin-4 as a novel negative soluble regulator in the timing of developmental myelination. Here, we investigated whether galectin-4 is re-expressed in axons upon demyelination to regulate the timing of remyelination. Our findings revealed that galectin-4 is transiently localized to axons in demyelinated areas upon cuprizone-induced demyelination. In contrast, in chronic demyelinated MS lesions, where remyelination fails, galectin-4 is permanently present on axons. Remarkably, microglia/macrophages in cuprizone-demyelinated areas also harbor galectin-4, as also observed in activated microglia/macrophages that are present in active MS lesions and in inflammatory infiltrates in chronic-relapsing experimental autoimmune encephalomyelitis. In vitro analysis showed that galectin-4 is effectively endocytosed by macrophages, and may scavenge galectin-4 from oligodendrocytes, and that endogenous galectin-4 levels are increased in alternatively interleukin-4-activated macrophages and microglia. Hence, similar to developmental myelination, the (re)expressed galectin-4 upon demyelination may act as factor in the timing of oligodendrocyte differentiation, while the persistent presence of galectin-4 on demyelinated axons may disrupt this fine-tuning of remyelination.
|Number of pages||15|
|Journal||Journal of neuropathology and experimental neurology|
|Early online date||24-Aug-2018|
|Publication status||Published - Nov-2018|
- Demyelination, Galectin-4, Macrophages, Microglia, Multiple sclerosis, Oligodendrocytes, Remyelination, CENTRAL-NERVOUS-SYSTEM, MYELIN MEMBRANE FORMATION, CELL-ADHESION MOLECULE, ANIMAL LECTINS, MACROPHAGE ACTIVATION, INDUCED DEMYELINATION, CNS DEMYELINATION, HUMAN MICROGLIA, FYN KINASE, SUGAR CODE