Actomyosin-II Proactively Shields Axons of the Central Nervous System from Mild Mechanical Stress

doi:10.1101/2023.08.09.552549

	Actomyosin-II Proactively Shields Axons of the Central Nervous System from Mild Mechanical Stress
	Pan, Xiaorong1 ; Lei, Gaowei 2; Li, Jie3,4 ; Luan, Tongshu1 ; Hu, Yiqing1 ; Chu, Yuanyuan1 ; Feng, Yu1 ; Zhan, Wenrong1 ; Zhao, Chunxia 5; Meunier, Frederic A.6,7; Liu, Yifan3,4 ; Li, Yi 2; Wang, Tong1
	2023-08-13
状态	已发表
摘要	Traumatic brain injury (TBI) remains a significant and unmet health challenge. However, our understanding of how neurons, particularly their fragile axons, withstand the abrupt mechanical impacts within the central nervous system remains largely unknown. Using a microfluidic device applying discrete levels of transverse forces to axons, we identified the stress levels that most axons could resist and explored their instant responses at nanoscale resolution. Mild stress induces rapid and reversible axon beading, driven by actomyosin-II-dependent radial contraction, which restricts the spreading and bursting of stress-induced Ca²⁺ waves. More severe stress causes irreversible focal swelling and Ca²⁺ overload, ultimately leading to focal axonal swelling and degeneration. Up-regulating actomyosin-II activity prevented the progression of initial injury in vivo, protecting commissural axons from degeneration in a mice TBI model. Our study established a scalable axon injury model and uncovered the critical roles of actomyosin-II in shielding neurons against detrimental mechanical stress.
语种	英语
DOI	10.1101/2023.08.09.552549
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:76454177
WOS类目	Neurosciences
资助项目	National Natural Science Foundation of China["LE130100078","SYLPOC0022022","GNT1155794","31871036"] ; Double First-Class Initiative Fund of ShanghaiTech University["32271001","SYLDX0302022","GNT1120381"] ; NHMRC Senior Research Fellowship[32100777]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/381327
专题	生命科学与技术学院物质科学与技术学院生命科学与技术学院_硕士生生命科学与技术学院_博士生物质科学与技术学院_博士生物质科学与技术学院_PI研究组_刘一凡组生命科学与技术学院_PI研究组_王彤组
通讯作者	Li, Yi; Wang, Tong
作者单位	1.ShanghaiTech Univ, Brain Ctr, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Chinese Acad Sci CAS China, Ctr Excellence Brain Sci & Intelligence Technol CEBSIT, Shanghai 200010, Peoples R China 3.ShanghaiTech Univ, Sch Phys Sci & Technol, Div Chem & Phys Biol, Shanghai 201210, Peoples R China 4.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China 5.Univ Adelaide, Sch Chem Engn, Adelaide, SA 5005, Australia 6.Univ Queensland, Queensland Brain Inst, Clem Jones Ctr Ageing Dementia Res, Brisbane, Qld 4072, Australia 7.Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia
推荐引用方式 GB/T 7714	Pan, Xiaorong,Lei, Gaowei,Li, Jie,et al. Actomyosin-II Proactively Shields Axons of the Central Nervous System from Mild Mechanical Stress. 2023.