Oxidative Stress and the CNS

Re: Symposium 783

On Sun Dec 6, grover wrote
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>Dr. Rice: Great presentation. Hope you have fun at the meeting. Do you think that these differences in relative concentrations of ascorbate and glutathione represent differences in the transport or metbaolism in these tissues? Which cells have large volume/area ratios and how would this affect transport densities/unit membrane vs. per cell?
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Dr. Grover -- Thanks for your interesting questions and for stimulating the discussion! Our data are consistent with the hypothesis that ascorbate is 10-fold more concentrated in neurons than in glia because of the higher rate of oxidative metabolism in neurons. Higher metabolic rate would mandate greater antioxidant protection, which we suggest is provided, at least in part, by ascorbate. Other labs have demonstrated greater GSH synthesis activity in glia, however, which is consistent with the slightly higher glial ascorbate content we found in our studies.

Cellular ascorbate levels are maintained by active uptake from the extracellular fluid, rather than intracellular ascorbate synthesis. Consequently, higher expression of an ascorbate transporter in neurons than in glia might underlie the differences in intracellular levels. Your point about differences in surface-to-volume ratio among cell types is well taken. This could contribute to differences in intracellualr concentration. However, I doubt that's the main controlling factor for two reasons: 1) granule cells in the cerebellum have a much higher surface-to-volume ratio than pyramidal cells in cerebral cortex, yet our data indicate that ascorbate levels are similar in both cell populations; and 2) surface-to-volume ratio differences among neuron populations are likely to vary as greatly as between the "average" neuron and the "average" glial cell.

More likely, as suggested above, the differences are caused by differences in expression level of ascorbate tranporters, or by modulation of activity by phosphorylation state or other regulatory mechanisms, or even by expression of distinct neuron and glial transport proteins. Unfortunately, little is known about about ascorbate transporter(s) at the molecular level, so these comments remain speculative at present.

Mon Dec 14