Localization of a glutathione-dependent dehydroascorbate reductase within the central nervous system of the rat

In this study, we describe for the first time the occurrence, within the ce ntral nervous system of the rat, of a dehydroascorbate reductase analogous to the one we recently described in the liver. Dehydroascorbate reductase p lays a pivotal role in regenerating ascorbic acid from its oxidation produc t, dehydroascorbate. In a first set of experiments, we showed that a dehydr oascorbate reductase activity is present in brain cytosol; immunoblotting a nalysis confirmed the presence of an immunoreactive cytosolic protein in se lected brain areas. Immunotitration showed that approximately 65% of dehydr oascorbate reductase activity of brain cytosol which was recovered in the a mmonium sulphate fraction can be attributed to this enzyme. Using immunohis tochemistry, we found that a variety of brain areas expresses the enzyme. I mmunoreactivity was confined to the gray matter. Amongst the several brain regions, the cerebellum appears to be the most densely stained. The enzyme was also abundant in the hippocampus and the olfactory cortex. The lesion o f norepinephrine terminals following systemic administration of DSP-4 marke dly decreased immunoreactivity in the cerebellum. Apart from the possible c o-localization of the enzyme with norepinephrine, the relative content of d ehydroascorbate reductase in different brain regions might be crucial in co nditioning regional sensitivity to free radical-induced brain damage. Given the scarcity of protective mechanisms demonstrated in the brain, the discovery of a new enzyme with antioxidant properties might represent a sta rting-point to increase our knowledge about the antioxidant mechanisms oper ating in several central nervous system disorders. (C) 1999 IBRO. Published by Elsevier Science Ltd.