Leptin sustains spontaneous remyelination in the adult central nervous system.
Leptin sustains spontaneous remyelination in the adult central nervous system.
复制标题
DOI：
10.1038/srep40397
复制
发表时间：
2017-01-16
影响因子：
4.6
通讯作者：
Yamashita T
中科院分区：
文献类型：
--
作者：
Matoba K;Muramatsu R;Yamashita T
脱髓鞘是许多中枢神经系统（CNS）疾病的共同特征，并与神经功能缺损相关。脱髓鞘的轴突依赖于少突胶质细胞的发育而自发地再髓鞘化，这主要涉及在CNS环境中表达的分子。在本研究中，我们发现瘦素，一种由脂肪细胞分泌的外周激素，促进少突胶质前体细胞（OPCs）的增殖。瘦素通过细胞外信号调节激酶（ERK）的体外磷酸化增加OPC增殖;而瘦素中和抑制OPC增殖和毒素诱导的脱髓鞘小鼠模型中的髓鞘再生。OPC特异性瘦素受体长亚型（LepRb）的缺失在小鼠中抑制OPC增殖和脱髓鞘反应中的髓鞘再生。鞘内瘦素给药增加OPC增殖。这些结果证明了一种新的分子机制，瘦素持续OPC增殖和髓鞘再生的病理中枢神经系统。
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.