1. Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model
- Author
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Yue Hao, Yinchun Su, Yifan He, Wenyuan Zhang, Yang Liu, Yu Guo, Xingfan Chen, Chunhan Liu, Siyu Han, Buyi Wang, Yushuang Liu, Wei Zhao, Lili Mu, Jinghua Wang, Haisheng Peng, Junwei Han, and Qingfei Kong
- Subjects
Dopamine ,Endothelial cells ,Central nervous system ,Tight junction ,Adherence junctions ,Wnt/β-catenin pathway ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood–brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/β-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain–blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/β-catenin pathway. Graphical Abstract
- Published
- 2024
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