ArticleProceedings of the National Academy of Sciences of the United States of America2020
Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- The effect of mindfulness interventions on stress in medical students: A systematic review and meta-analysis.PloS one · 2023Pooled it
- Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.Neural regeneration research · 2026Article
- Astrocyte-Derived Extracellular Vesicles and the Evolution of Neural Complexity: Perspectives on Vesicle-Mediated Neuron-Glia Communication.Molecular neurobiology · 2026Review
- Article
- Higher fasting brain glucose is associated with lower gray matter volume in healthy adults.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
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- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- The 5-HT1A receptor antagonist WAY-100635 maleate promotes retinal ganglion cell differentiation and protects the retino-visual circuits.Communications medicine · 2026Article
- CREB3L1 Modulates Extracellular Matrix Gene Expression and Proliferation in Glaucomatous Lamina Cribrosa Cells.Biomedicines · 2026Article
- The rise of astrocytes: are they guardians or troublemakers of the brain disorder?Experimental & molecular medicine · 2026Review
- Inhibition of connexin hemichannels protects retinal ganglion cells against ocular nerve injury.Cellular and molecular life sciences : CMLS · 2026Article
- Bridging Hypoxia and Vision Loss: The Emerging Role of Connexins in Local and Systemic Eye Diseases.International journal of molecular sciences · 2026Review
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- Compression injury regulates astrocyte morphology, metabolic function, and extracellular matrix modification in a 3D hydrogel.bioRxiv : the preprint server for biology · 2025Article
- Zebrafish optic nerve injury results in systemic retinal ganglion cell dedifferentiation.PLoS genetics · 2025Article
- A High-Fidelity RNA-Targeting Cas13X Downregulates Connexin43 in Macroglia: A Novel Neuroprotective Strategy for Glaucoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.Glia · 2025Article
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke.Nature communications · 2025Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.