气候变化领域集成服务门户(CCPortal): Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress

CCPortal

DOI	10.1073/pnas.2009425117
	Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress
	Cooper M.L.; Pasini S.; Lambert W.S.; D'Alessandro K.B.; Yao V.; Risner M.L.; Calkins D.J.
发表日期	2020
ISSN	0027-8424
起始页码	18810
结束页码	18821
卷号	117 期号:31
英文摘要	In the central nervous system, glycogen-derived bioenergetic resources in astrocytes help promote tissue survival in response to focal neuronal stress. However, our understanding of the extent to which these resources are mobilized and utilized during neurodegeneration, especially in nearby regions that are not actively degenerating, remains incomplete. Here we modeled neurodegeneration in glaucoma, the world's leading cause of irreversible blindness, and measured how metabolites mobilize through astrocyte gap junctions composed of connexin 43 (Cx43). We elevated intraocular pressure in one eye and determined how astrocyte-derived metabolites in the contralateral optic projection responded. Remarkably, astrocyte networks expand and redistribute metabolites along distances even 10 mm in length, donating resources from the unstressed to the stressed projection in response to intraocular pressure elevation. While resource donation improves axon function and visual acuity in the directly stressed region, it renders the donating tissue susceptible to bioenergetic, structural, and physiological degradation. Intriguingly, when both projections are stressed in a WT animal, axon function and visual acuity equilibrate between the two projections even when each projection is stressed for a different length of time. This equilibration does not occur when Cx43 is not present. Thus, Cx43-mediated astrocyte metabolic networks serve as an endogenous mechanism used to mitigate bioenergetic stress and distribute the impact of neurodegenerative disease processes. Redistribution ultimately renders the donating optic nerve vulnerable to further metabolic stress, which could explain why local neurodegeneration does not remain confined, but eventually impacts healthy regions of the brain more broadly. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Astrocyte; Astrocyte network; Gap junction; Metabolism; Neurodegeneration
语种	英语
scopus关键词	connexin 43; connexin 43; adult; animal experiment; animal tissue; Article; astrocyte; bioenergy; blindness; cell function; cell metabolism; controlled study; degenerative disease; glaucoma; intraocular pressure; male; mouse; nerve cell network; nerve degeneration; nonhuman; pressure measurement; priority journal; visual acuity; animal; astrocyte; C57BL mouse; degenerative disease; female; gap junction; genetics; metabolism; physiology; transgenic mouse; Animals; Astrocytes; Connexin 43; Female; Gap Junctions; Glaucoma; Intraocular Pressure; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160244
作者单位	Cooper, M.L., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; Pasini, S., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; Lambert, W.S., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; D'Alessandro, K.B., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; Yao, V., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; Risner, M.L., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States; Calkins, D.J., Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-0654, United States
推荐引用方式 GB/T 7714	Cooper M.L.,Pasini S.,Lambert W.S.,et al. Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress[J],2020,117(31).
APA	Cooper M.L..,Pasini S..,Lambert W.S..,D'Alessandro K.B..,Yao V..,...&Calkins D.J..(2020).Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress.Proceedings of the National Academy of Sciences of the United States of America,117(31).
MLA	Cooper M.L.,et al."Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress".Proceedings of the National Academy of Sciences of the United States of America 117.31(2020).