Abstract：
With the improvement of cancer treatment techniques, increasing attention has been given to chemotherapy-induced cognitive impairment through white matter injury. Clemastine fumarate has been shown to enhance white matter integrity in cuprizone- or hypoxia-induced demyelination mouse models. However, whether clemastine can be beneficial for reversing chemotherapy-induced cognitive impairment remains unexplored. In this study, the mice received oral administration of clemastine after chemotherapy. The open-field test and Morris water maze test were used to evaluate their anxiety, locomotor activity and cognitive function. Luxol Fast Blue staining and transmission electron microscopy were used to detect the morphological damage to the myelin. Demyelination and damage to the mature oligodendrocytes and axons were observed by immunofluorescence and western blotting. Clemastine significantly improved their cognitive function and ameliorated white matter injury in the chemotherapy-treated mice. Clemastine enhanced myelination, promoted oligodendrocyte precursor cell differentiation and increased the neurofilament 200 protein levels in the corpus callosum and hippocampus. We concluded that clemastine rescues cognitive function damage caused by chemotherapy through improving white matter integrity. Remyelination, oligodendrocyte differentiation and the increase of neurofilament protein promoted by clemastine are potential strategies for reversing the cognitive dysfunction caused by chemotherapy.
摘要：
随着癌症治疗技术的提高，化疗引起的脑白质损伤引起的认知障碍受到越来越多的关注.已显示富马酸氯马斯汀可增强铜氮或缺氧诱导的脱髓鞘小鼠模型中的白质完整性。然而,氯马斯汀是否有利于逆转化疗诱导的认知障碍仍有待研究.在这项研究中,化疗后，小鼠口服氯马斯汀。采用开场试验和Morris水迷宫试验评价其焦虑,运动活动和认知功能。LuxolFastBlue染色和透射电子显微镜用于检测髓鞘的形态损伤。通过免疫荧光和蛋白质印迹观察到成熟少突胶质细胞和轴突的脱髓鞘和损伤。在化疗的小鼠中，氯马斯汀显着改善了其认知功能并改善了白质损伤。氯马斯汀增强髓鞘形成，促进少突胶质细胞前体细胞分化，并增加call体和海马中神经丝200蛋白的水平。我们得出的结论是，氯马斯汀通过改善脑白质完整性来挽救化疗引起的认知功能损害。髓鞘再生,氯马斯汀促进少突胶质细胞分化和神经丝蛋白的增加是逆转化疗引起的认知功能障碍的潜在策略。
