Microglial EPOR Contribute to Sevoflurane-induced Developmental Fine Motor Deficits Through Synaptic Pruning in Mice.
10.1007/s12264-024-01248-5
- Author:
Danyi HE
1
;
Xiaotong SHI
1
;
Lirong LIANG
1
;
Youyi ZHAO
1
;
Sanxing MA
1
;
Shuhui CAO
1
;
Bing LIU
1
;
Zhenzhen GAO
1
;
Xiao ZHANG
1
;
Ze FAN
2
,
3
;
Fang KUANG
4
;
Hui ZHANG
3
,
5
Author Information
1. State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.
2. State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China. fanze3584@
3. com.
4. Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China. kuangf@fmmu.edu.cn.
5. State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China. zhanghuifmmua@
- Publication Type:Journal Article
- Keywords:
Erythropoietin;
Fine motor deficits;
Microglia;
Sevoflurane;
Synaptic pruning
- MeSH:
Animals;
Sevoflurane/toxicity*;
Microglia/drug effects*;
Anesthetics, Inhalation/adverse effects*;
Mice;
Mice, Inbred C57BL;
Receptors, Erythropoietin/metabolism*;
Neuronal Plasticity/drug effects*;
Male;
Prefrontal Cortex/drug effects*;
Erythropoietin/pharmacology*;
Signal Transduction/drug effects*
- From:
Neuroscience Bulletin
2024;40(12):1858-1874
- CountryChina
- Language:English
-
Abstract:
Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
