Cordycepin (3′-deoxyadenosine) promotes remyelination via suppression of neuroinflammation in a cuprizone-induced mouse model of demyelination
Cordycepin (3′-deoxyadenosine) promotes remyelination via suppression of neuroinflammation in a cuprizone-induced mouse model of demyelination
复制标题
虫草素（3'-脱氧腺苷）通过抑制铜宗诱导的脱髓鞘小鼠模型中的神经炎症来促进髓鞘再生
DOI：
10.1016/j.intimp.2019.105777
复制
发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Du, Jing
中科院分区：
文献类型：
--
作者：
Jia, Yue;Li, Haoran;Du, Jing
多发性硬化症（MS）是一种以自身免疫损伤中枢神经系统为特征的炎症性脱髓鞘疾病。在这种疾病中，髓鞘再生失败可能导致持续性残疾。虫草素，也被称为3'-脱氧腺苷，具有抗炎、抗氧化、抗凋亡和神经保护作用。铜酮（CPZ）模型由于能模拟脱髓鞘疾病的一些特征而被广泛应用于MS的研究。为了确定虫草素是否促进cpz诱导脱髓鞘后的再髓鞘形成和功能恢复，我们给cpz诱导脱髓鞘小鼠注射虫草素。虫草素逆转cpz诱导的体重下降，并挽救模型小鼠的运动功能障碍。虫草素能有效促进胼胝体髓鞘再生，增强MBP的表达。虫草素还能抑制cpz诱导的胼胝体和大脑皮层中iba1阳性小胶质细胞、gfap阳性星形胶质细胞和olig2阳性少突胶质前体细胞数量的增加。虫草素治疗后，胼胝体和海马中促炎细胞因子IL-1 β和IL-6表达受到抑制，抗炎细胞因子IL-4和神经营养因子BDNF释放升高。此外，我们还发现虫草素改善了cpz诱导的体重减轻、运动功能障碍、脱髓鞘、胼胝体和海马中胶质细胞活化和促炎细胞因子的表达。我们的研究结果表明，虫草素可能通过抑制神经炎症而成为脱髓鞘相关疾病的有用治疗剂。
Multiple sclerosis (MS) is an inflammatory demyelination disease characterized by autoimmune damage to the central nervous system. In this disease, failure of remyelination could cause persistent disability. Cordycepin, also known as 3'-deoxyadenosine, exerts anti-inflammatory, anti-oxidic, anti-apoptotic and neuroprotective effects. The cuprizone (CPZ) model has been widely used to study MS as it mimics some characteristics of demyelination disease. To determine whether cordycepin promotes remyelination and functional recovery after CPZ-induced demyelination, we administered cordycepin to the CPZ-induced demyelination mice. Cordycepin reversed CPZ-induced loss of body weight and rescued motor dysfunction in the model mice. Cordycepin effectively promoted remyelination and enhanced MBP expression in the corpus callosum. Cordycepin also inhibited the CPZ-induced increase in the number of Iba1-positive microglia, GFAP-positive astrocytes and Olig2-positive oligodendroglial precursor cells in the corpus callosum and cerebral cortex. Pro-inflammatory cytokine expression (IL-1 beta and IL-6) was inhibited while anti-inflammatory cytokine IL-4 and neurotrophic factor BDNF release was elevated in the corpus callosum and hippocampus after cordycepin treatment. In addition, we also found that cordycepin ameliorated CPZ-induced body weight loss, motor dysfunction, demyelination, glial cells activation and pro-inflammatory cytokine expression in the corpus callosum and hippocampus. Our results suggest that cordycepin may represent a useful therapeutic agent in demyelination-related diseases via suppression of neuroinflammation.