Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
Sci Rep. 2017 Jan 16;7:40397. doi: 10.1038/srep40397.
Demyelination is a common feature of many central nervous system (CNS) diseases and is associated with neurological impairment. Demyelinated axons are spontaneously remyelinated depending on oligodendrocyte development, which mainly involves molecules expressed in the CNS environment. In this study, we found that leptin, a peripheral hormone secreted from adipocytes, promoted the proliferation of oligodendrocyte precursor cells (OPCs). Leptin increased the OPC proliferation via in vitro phosphorylation of extracellular signal regulated kinase (ERK); whereas leptin neutralization inhibited OPC proliferation and remyelination in a mouse model of toxin-induced demyelination. The OPC-specific leptin receptor long isoform (LepRb) deletion in mice inhibited both OPC proliferation and remyelination in the response to demyelination. Intrathecal leptin administration increased OPC proliferation. These results demonstrated a novel molecular mechanism by which leptin sustained OPC proliferation and remyelination in a pathological CNS.
脱髓鞘是许多中枢神经系统 (CNS) 疾病的共同特征，与神经功能损伤有关。脱髓鞘轴突可在少突胶质细胞发育的情况下自发进行髓鞘修复，这主要涉及中枢神经系统环境中表达的分子。在这项研究中，我们发现瘦素，一种由脂肪细胞分泌的外周激素，可促进少突胶质前体细胞 (OPC) 的增殖。瘦素通过体外细胞外信号调节激酶 (ERK) 的磷酸化来增加 OPC 的增殖；而瘦素中和则抑制毒素诱导的脱髓鞘模型中的 OPC 增殖和髓鞘修复。在对脱髓鞘的反应中，敲除小鼠的 OPC 特异性瘦素受体长型 (LepRb) 可同时抑制 OPC 的增殖和髓鞘修复。鞘内给予瘦素可增加 OPC 的增殖。这些结果表明了一种新的分子机制，通过该机制，瘦素在病理性中枢神经系统中维持 OPC 的增殖和髓鞘修复。
