Moradbeygi Khadijeh, Parviz Mohsen, Rezaeizadeh Hossein, Zargaran Arman, Sahraian Mohammad Ali, Mehrabadi Shima, Nikbakhtzadeh Marjan, Zahedi Elham
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, Department of Nursing, Abadan Faculty of Medical Sciences, Abadan, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2021 Jul;24(7):900-907. doi: 10.22038/ijbms.2021.53531.12043.
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.
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.
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.
These results provide evidence that LINGO-1 antibody can improve remyelination and neurobehavioral deficit.
中枢神经系统脱髓鞘是多发性硬化症（MS）的主要特征。MS 中尚未满足的最重要需求是使用能够延缓疾病进展的治疗方法。富含亮氨酸重复序列和免疫球蛋白样结构域的 NOGO 受体相互作用蛋白 1（LINGO-1）已被认为是少突胶质细胞分化和髓鞘形成的抑制剂。
我们使用 cuprizone 诱导的脱髓鞘来研究 LINGO-1 抗体对髓鞘再生和神经行为缺陷的影响。将动物随机分为三组（n = 10）：（1）对照组；给予常规饮食，（2）CPZ 组；腹腔注射生理盐水，（3）治疗组；每六天腹腔注射一次 LINGO-1 抗体（10 mg/kg），共 3 周。我们通过针对髓鞘碱性蛋白（MBP）、神经丝重链（NF200）和脑源性神经保护因子（BDNF）的免疫染色来评估胼胝体（CC）中 MBP、NF200 和 BDNF 的水平。
我们发现脱髓鞘的 CC 中 MBP、NF200 和 BDNF 的水平降低，抗 LINGO-1 治疗改善了脱髓鞘结构。此外，通过旷场试验（OFT）和平衡木试验测量运动障碍。在治疗组中，运动障碍得到显著改善。
这些结果提供了证据，表明 LINGO-1 抗体可以改善髓鞘再生和神经行为缺陷。
