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Altered Energy Metabolism During Early Optic Nerve Crush Injury: Implications of Warburg-Like Aerobic Glycolysis in Facilitating Retinal Ganglion Cell Survival
- Source :
- Neuroscience Bulletin
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Neurons, especially axons, are metabolically demanding and energetically vulnerable during injury. However, the exact energy budget alterations that occur early after axon injury and the effects of these changes on neuronal survival remain unknown. Using a classic mouse model of optic nerve-crush injury, we found that traumatized optic nerves and retinas harbor the potential to mobilize two primary energetic machineries, glycolysis and oxidative phosphorylation, to satisfy the robustly increased adenosine triphosphate (ATP) demand. Further exploration of metabolic activation showed that mitochondrial oxidative phosphorylation was amplified over other pathways, which may lead to decreased retinal ganglion cell (RGC) survival despite its supplement to ATP production. Gene set enrichment analysis of a microarray (GSE32309) identified significant activation of oxidative phosphorylation in injured retinas from wild-type mice compared to those from mice with deletion of phosphatase and tensin homolog (PTEN), while PTEN-/- mice had more robust RGC survival. Therefore, we speculated that the oxidation-favoring metabolic pattern after optic nerve-crush injury could be adverse for RGC survival. After redirecting metabolic flux toward glycolysis (magnifying the Warburg effect) using the drug meclizine, we successfully increased RGC survival. Thus, we provide novel insights into a potential bioenergetics-based strategy for neuroprotection. Electronic supplementary material The online version of this article (10.1007/s12264-020-00490-x) contains supplementary material, which is available to authorized users.
- Subjects :
- Male
Retinal Ganglion Cells
0301 basic medicine
Optic nerve crush
Cell Survival
Physiology
Oxidative phosphorylation
Biology
Neuroprotection
Crush Injuries
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
Glycolysis
Mice, Knockout
General Neuroscience
Optic Nerve
General Medicine
Warburg effect
Axons
Cell biology
Mice, Inbred C57BL
ATP
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
chemistry
Retinal ganglion cell
Anaerobic glycolysis
Optic Nerve Injuries
Optic nerve
Original Article
sense organs
Energy Metabolism
Adenosine triphosphate
030217 neurology & neurosurgery
RGC survival
Subjects
Details
- ISSN :
- 19958218 and 16737067
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Neuroscience Bulletin
- Accession number :
- edsair.doi.dedup.....8a2809584c7371ea5877c3fddd3e4f1c