Anti-LINGO -1 improved remyelination and neurobehavioral deficit in cuprizone-induced demyelination

Abstract

Objective(s): Central nervous system demyelination is the main feature of multiple sclerosis (MS). The most important unmet need in MS is use of treatments that delay the progression of the disease. Leucine-rich repeat and Immunoglobulin-like domain containing NOGO receptor-interacting protein 1(LINGO-1) have been known as inhibitors of oligodendrocyte differentiation and myelination.Materials and Methods: We investigated LINGO-1 antibody effects on remyelination and neurobehavioral deficit using cuprizone-induced demyelination. Animals were randomly divided into three groups (n = 10): (1) Control group; received the regular diet, (2) CPZ group; normal saline was injected intraperitoneally, and (3) Treatment group; LINGO-1 antibody (10 mg/kg) was injected IP once every six days for 3 weeks. We assessed the level of myelin basic protein (MBP), neurofilament heavy chain (NF200), and Brain-derived neuroprotective factor (BDNF) in the corpus callosum (CC) by immunostaining against MBP, NF200, and BDNF. Results: We found decreased levels of MBP, NF200, and BDNF in demyelinated CC, and anti-LINGO-1 treatment improved demyelinated structures. Furthermore, motor impairment was measured by Open-field (OFT) and Balance beam tests. In the treatment group, motor impairment was significantly improved. Conclusion: These results provide evidence that LINGO-1 antibody can improve remyelination and neurobehavioral deficit.

Keywords

• brain-derived neurotrophic factor
• cuprizone
• multiple sclerosis
• myelin basic protein
• nogo receptor 1
• remyelination