Membrane Associated RNA-Containing Vesicles Regulate Cortical Astrocytic Microdomain Calcium Transients in Awake Ischemic Stroke Mice

被引:0
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作者
Zhou, Zhongqiu [1 ]
Bai, Ying [1 ]
Gu, Xiaochun [2 ]
Ren, Hui [1 ]
Xi, Wen [1 ]
Wang, Yu [1 ]
Bian, Liang [1 ]
Liu, Xue [1 ]
Shen, Ling [1 ]
Xiang, Xianyuan [3 ]
Huang, Wenhui [4 ]
Luo, Zhuojuan [5 ]
Han, Bing [1 ]
Yao, Honghong [1 ,6 ,7 ]
机构
[1] Southeast Univ, Sch Med, Dept Pharmacol, Jiangsu Prov Key Lab Crit Care Med, Nanjing 210009, Peoples R China
[2] Southeast Univ, Zhongda Hosp, Med Sch, Dept Radiol,Jiangsu Key Lab Mol & Funct Imaging, Nanjing 210009, Peoples R China
[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China
[4] Univ Saarland, Ctr Integrat Physiol & Mol Med, Dept Mol Physiol, D-66421 Homburg, Germany
[5] Southeast Univ, Sch Life Sci & Technol, Key Lab Dev Genes & Human Dis, Nanjing 210096, Peoples R China
[6] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226001, Peoples R China
[7] Southeast Univ, Inst Life Sci, Key Lab Dev Genes & Human Dis, Nanjing 210096, Peoples R China
基金
中国国家自然科学基金;
关键词
astrocytic microdomain calcium transients; circSCMH1; ischemic stroke; membrane associated RNA-containing vesicles; mitochondria; PERIINFARCT DEPOLARIZATIONS; CA2+ TRANSIENTS; RELEASE; INJURY; PLASTICITY; CHANNELS;
D O I
10.1002/advs.202404391
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision-tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca2+) transients in astrocytic processes are pivotal for the functional regulation of these processes. However, the understanding of the alterations and regulatory mechanism of microdomain Ca2+ transients during stroke remains limited. In the present study, a fast high-resolution, miniaturized two-photon microscopy is used to show that the levels of astrocytic microdomain Ca2+ transients are significantly reduced in the peri-infarct area of awake ischemic stroke mice. This finding correlated with the behavioral deficits shown by these mice under freely-moving conditions. Mitochondrial Ca2+ activity is an important factor driving the microdomain Ca2+ transients. DEAD Box 1 (DDX1) bound to circSCMH1 (a circular RNA involved in vascular post-stroke repair) facilitates the formation of membrane-associated RNA-containing vesicles (MARVs) and enhances the activity of astrocytic microdomain Ca2+ transients, thereby promoting behavioral recovery. These results show that targeting astrocytic microdomain Ca2+ transients is a potential therapeutic approach in stroke intervention.
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页数:18
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