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• W3044202555 endingPage "18821" @default.
• W3044202555 startingPage "18810" @default.
• W3044202555 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 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." @default.
• W3044202555 created "2020-07-29" @default.
• W3044202555 creator A5006378558 @default.
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• W3044202555 creator A5074518877 @default.
• W3044202555 creator A5076526686 @default.
• W3044202555 creator A5091095249 @default.
• W3044202555 date "2020-07-20" @default.
• W3044202555 modified "2023-10-16" @default.
• W3044202555 title "Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress" @default.
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• W3044202555 doi "https://doi.org/10.1073/pnas.2009425117" @default.
• W3044202555 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7414143" @default.
• W3044202555 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32690710" @default.
• W3044202555 hasPublicationYear "2020" @default.
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