Institute of Neuroscience, Chongqing Medical University Basic Medical College, Chongqing 400016, China.
Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Neuroscience. 2022 Feb 21;484:66-79. doi: 10.1016/j.neuroscience.2022.01.001. Epub 2022 Jan 7.
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.
随着癌症治疗技术的提高，人们越来越关注化疗引起的白质损伤导致的认知障碍。富马酸氯马斯汀已被证明能增强杯状朊病毒或低氧诱导的脱髓鞘小鼠模型中的白质完整性。然而，富马酸氯马斯汀是否能有益于逆转化疗引起的认知障碍仍未被探索。在这项研究中，小鼠在化疗后接受富马酸氯马斯汀的口服给药。通过旷场试验和 Morris 水迷宫试验来评估它们的焦虑、运动活性和认知功能。通过 Luxol Fast Blue 染色和透射电子显微镜检测髓鞘的形态损伤。通过免疫荧光和蛋白质印迹法观察脱髓鞘和成熟少突胶质细胞和轴突的损伤。富马酸氯马斯汀显著改善了化疗处理的小鼠的认知功能并减轻了白质损伤。富马酸氯马斯汀增强了髓鞘形成，促进了少突胶质前体细胞的分化，并增加了胼胝体和海马中的神经丝 200 蛋白水平。我们得出结论，富马酸氯马斯汀通过改善白质完整性来挽救化疗引起的认知功能损伤。富马酸氯马斯汀促进的髓鞘形成、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。
