advertisement
Abstract #90128 Published in IGR 21-3
Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress
Cooper ML; Pasini S; Lambert WS; D'Alessandro KB; Yao V; Risner ML; Calkins DJProceedings of the National Academy of Sciences of the United States of America 2020; 117: 18810-18821
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.
Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville TN 37232-0654.
Full articleClassification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.15 Optic nerve (Part of: 2 Anatomical structures in glaucoma)
2.16 Chiasma and retrochiasmal central nervous system (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
