The neuroprotective mechanism of lithium after ischaemic stroke
| Autor: | Xinyu Li, Baoman Li, Ming Ji, Wenliang Gong, Huiya Yuan, Alexei Verkhratsky, Benjie Chen, Maosheng Xia, Manman Zhang, Beina Chen, Chengyi Dong, Yuefei Zhou, Xiafang Wu, Dianjun Zhang, Gehua Wen, Enyu Xu, Xiaoni Zhan |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Lithium (medication) QH301-705.5 Medicine (miscellaneous) Mice Transgenic Pharmacology Lithium Neuroprotection General Biochemistry Genetics and Molecular Biology Mice Random Allocation Ischaemic stroke Medicine Animals Cognitive Dysfunction RNA Messenger Biology (General) Ischemic Stroke business.industry Mechanism (biology) Depression Neuroprotective Agents Gene Expression Regulation business General Agricultural and Biological Sciences medicine.drug |
| Zdroj: | Communications Biology, Vol 5, Iss 1, Pp 1-14 (2022) |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-022-03051-2 |
| Popis: | Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li+), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We found that Li+ inhibits activation of nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the middle cerebral artery occlusion (MCAO) stroke model in mice. This action of Li+ is mediated by two signalling pathways of AKT/GSK3β/β-catenin and AKT/FoxO3a/β-catenin which converge in suppressing the production of reactive oxygen species (ROS). Using immunocytochemstry, MRI imaging, and cell sorting with subsequent mRNA and protein quantification we demonstrate that Li+ decreases the infarct volume, improves motor function, and alleviates associated cognitive and depressive impairments. In conclusion, this study reveals molecular mechanisms of Li+ neuroprotection during brain ischaemia thus providing the theoretical background to extend clinical applications of Li+ for treatment of ischemic stroke. |
| Databáze: | OpenAIRE |
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