LESS INDUCED 1-METHYL-4-PHENYLPYRIDINIUM ION NEUROTOXICITY ON STRIATAL SLICES FROM GUINEA-PIGS FED WITH A VITAMIN-C-DEFICIENT DIET

The effect of ascorbic acid depletion on the 1-methyl-4-phenylpyridini um ion (MPP(+))-induced neurotoxicity in the dopaminergic system has b een tested in guinea-pig striatal slices. Guinea-pigs were divided int o three groups and fed on a control diet, ascorbic acid-free diet and ascorbic acid-supplemented diet, respectively. Diets were maintained d uring 30 days. Striatal slices from ascorbic acid-deficient animals sh owed the highest levels of dopamine following 25 mu M MPP(+) treatment ; the results from animals under this treatment condition were statist ically different from both control and ascorbic acid-supplemented anim als under identical experimental conditions. In addition, neurochemica l analysis demonstrated that the levels of ascorbic acid and dehydroas corbic acid were highly reduced in striatal tissue from ascorbic acid- deficient animals, thus proving scorbutic conditions in our experiment al animals. In view of the higher resistance of the ascorbic acid-defi cient animals to the neurotoxicity elicited by MPP(+), additional dopa minergic parameters were also measured in striatal tissue from ascorbi c acid-deficient animals in the absence of MPP(+), including levels of dopamine and its metabolites, tyrosine hydroxylase activity and dopam ine uptake, with the aim of finding an explanation for this unexpected result. While dopamine levels and tyrosine hydroxylase activity remai ned close to control levels, dopamine uptake was significantly reduced in striatal synaptosomes from ascorbic acid-deficient animals as comp ared with control animals. Since MPP(+) is actively accumulated into d opaminergic nerve terminals via the high-affinity dopamine uptake syst em, this finding could explain the higher resistance of ascorbic acid- deficient animals to the dopamine-depleting effect induced by MPP(+) t oxicity assayed in striatal slices.