Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress

Proceedings of the National Academy of Sciences of the United States of America
Melissa L CooperDavid J Calkins

Abstract

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 pro...Continue Reading

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Citations

Feb 11, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Catherine Vignal-ClermontJosé-Alain Sahel
Dec 4, 2020·Current Ophthalmology Reports·Lauren K WarehamDavid J Calkins
Dec 11, 2020·Science Translational Medicine·Patrick Yu-Wai-ManJosé-Alain Sahel
Jan 29, 2021·Frontiers in Cellular Neuroscience·Michael L RisnerDavid J Calkins
Oct 30, 2020·Frontiers in Immunology·Mathias Linnerbauer, Veit Rothhammer
Feb 16, 2021·Frontiers in Cellular Neuroscience·Matthew J Van HookJennie C Smith
Mar 1, 2021·Progress in Retinal and Eye Research·David J Calkins
Mar 27, 2021·Mechanisms of Ageing and Development·Julie A Chowen, Luis M Garcia-Segura
Nov 11, 2020·Experimental Eye Research·Bailey G HannonMachelle T Pardue
May 1, 2021·International Journal of Molecular Sciences·Sara Al Hussein Al AwamlhDavid J Calkins
Jun 7, 2021·Molecular Neurodegeneration·Michael L RisnerDavid J Calkins
Jun 15, 2021·Frontiers in Neuroscience·Xiaohuan ZhaoXiaodong Sun
Jun 15, 2021·Frontiers in Molecular Neuroscience·Xiaomin HuangChenju Yi
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Sep 14, 2021·Cellular and Molecular Neurobiology·Kumari PreetiValencia Fernandes
Sep 30, 2021·International Ophthalmology Clinics·José-Alain SahelMagali Taiel

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Methods Mentioned

BETA
Conditional Knockout
genotyping
PCR
transgenic
Assay

Software Mentioned

GraphPad
Systat
SigmaPlot

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