Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 81, Issue 5, Pages 644-652Publisher
WILEY
DOI: 10.1002/jnr.20573
Keywords
glycogen; mouse optic nerve; L-lactate; glucose
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Funding
- NIDCR NIH HHS [DE13531] Funding Source: Medline
- NINDS NIH HHS [NS15586] Funding Source: Medline
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It is hypothesized that L-lactate derived from astrocyte glycogen sustains axon excitability in mouse optic nerve (MON). This theory was tested by using a competitive antagonist of L-lactate transport and immunocoochemistry to determine whether transport proteins are appropriately distributed in adult MON. L-lactate sustained the compound action potential (CAP), indicating that exogenous L-lactate was an effective energy substrate. During 60 min of aglycemia, the CAP persisted for 30 min, surviving on a glyco 11 g on-derived substrate (probably lactate), before failing. After failing,the CAP could be partially rescued by restoring 10 mM glucose or 20 mM L-lactate. Aglycemia in the presence of 20 mM D-lactate, a metabolically inert but transportable monocarboxylate, resulted in accelerated CAP decline compared with aglycemia alone, suggesting that D-lactate blocked the axonal uptake of glycogen-derived L-lactate, speeding the onset of energy failure and loss of the CAR The CAP was maintained for up to 2 hr when exposed to 20% of normal bath glucose (i.e., 2 mM). To test whether glycogen-derived L-lactate supplemented available glucose (2 mM) in supporting metabolism, L-lactate uptake into axons was reduced by the competitive inhibitor D-lactate. Indeed, in the presence of 20 mM D-lactate, the CAP was lost more rapidly in MONs bathed in 2 mM glucose artificial cerebrospinal fluid. Immunocytochemical staining demonstrated cell-specific expression of monocarboxylate transporter (MCT) subtypes, localizing MCT2 predominantly to axons and MCT1 predominantly to astrocytes, supporting the idea that L-lactate is released from astrocytes and taken up by axons as an energy source for sustaining axon excitability. (c) 2005 Wiley-Liss,inc.
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