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Metabolic substrates other than glucose support axon function in central white matter
A M Brown1, R Wender, B R Ransom
1Department of Neurology, Box 356465, University of Washington School of Medicine, Seattle, WA 98195, USA. ambrown@u.washington.edu
Journal of Neuroscience Research
|December 18, 2001
Summary
Non-glucose energy sources like lactate and pyruvate can effectively support central nervous system (CNS) axon function. This finding broadens our understanding of energy metabolism in myelinated axons.
Area of Science:
- Neuroscience
- Cellular Metabolism
- Neurobiology
Background:
- Axon function in the central nervous system (CNS) is primarily thought to depend on glucose metabolism.
- Understanding alternative energy substrates is crucial for comprehending neuronal health and disease.
Purpose of the Study:
- To investigate the capacity of various non-glucose energy sources to maintain axon function in the rat optic nerve.
- To identify specific metabolic pathways supporting CNS myelinated axon viability.
Main Methods:
- Assessment of axon function using stimulus-evoked compound action potential (CAP) monitoring in isolated rat optic nerve.
- Incubation of optic nerve explants with different energy substrates (glucose, lactate, pyruvate, fructose, mannose, glutamine, beta-hydroxybutyrate, octanoate, sorbitol, alanine, aspartate, glutamate) at specified concentrations.
- Maintenance of CAP amplitude over a 2-hour period to evaluate substrate support.
Main Results:
- Glucose, lactate, pyruvate, fructose, and mannose effectively supported full CAP amplitude for 2 hours.
- Glutamine provided partial support for axon function.
- Beta-hydroxybutyrate, octanoate, sorbitol, alanine, aspartate, and glutamate failed to support axon function.
- Lactate, pyruvate, and glutamine appear to be directly utilized by axons.
- Mannose and fructose may be metabolized via astrocytes to lactate for axonal energy supply.
Conclusions:
- A diverse range of compounds, beyond glucose, can sustain the function of CNS myelinated axons.
- Axons possess metabolic flexibility, utilizing various substrates for energy.
- Astrocytic-axonal metabolic coupling may play a role in energy provision for certain substrates like mannose and fructose.
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