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Less induced 1-methyl-4-phenylpyridinium ion neurotoxicity on striatal slices from guinea-pigs fed with a vitamin C-deficient diet.
MedLine Citation:
PMID:  9044384     Owner:  NLM     Status:  MEDLINE    
The effect of ascorbic acid depletion on the 1-methyl-4-phenylpyridinium ion (MPP+)-induced neurotoxicity in the dopaminergic system has been tested in guinea-pig striatal slices. Guinea-pigs were divided into three groups and fed on a control diet, ascorbic acid-free diet and ascorbic acid-supplemented diet, respectively. Diets were maintained during 30 days. Striatal slices from ascorbic acid-deficient animals showed the highest levels of dopamine following 25 microM MPP+ treatment; the results from animals under this treatment condition were statistically different from both control and ascorbic acid-supplemented animals under identical experimental conditions. In addition, neurochemical analysis demonstrated that the levels of ascorbic acid and dehydroascorbic acid were highly reduced in striatal tissue from ascorbic acid-deficient animals, thus proving scorbutic conditions in our experimental animals. In view of the higher resistance of the ascorbic acid-deficient animals to the neurotoxicity elicited by MPP+, additional dopaminergic parameters were also measured in striatal tissue from ascorbic acid-deficient animals in the absence of MPP+, including levels of dopamine and its metabolites, tyrosine hydroxylase activity and dopamine uptake, with the aim of finding an explanation for this unexpected result. While dopamine levels and tyrosine hydroxylase activity remained close to control levels, dopamine uptake was significantly reduced in striatal synaptosomes from ascorbic acid-deficient animals as compared with control animals. Since MPP+ is actively accumulated into dopaminergic nerve terminals via the high-affinity dopamine uptake system, this finding could explain the higher resistance of ascorbic acid-deficient animals to the dopamine-depleting effect induced by MPP+ toxicity assayed in striatal slices.
M Revuelta; M Romero-Ramos; J L Venero; F Millan; A Machado; J Cano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroscience     Volume:  77     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-05-02     Completed Date:  1997-05-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  167-74     Citation Subset:  IM    
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
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MeSH Terms
1-Methyl-4-phenylpyridinium / toxicity*
3,4-Dihydroxyphenylacetic Acid / metabolism
Amino Acids / metabolism
Ascorbic Acid Deficiency / metabolism*
Body Weight
Central Nervous System Diseases / chemically induced*,  metabolism
Dehydroascorbic Acid / metabolism
Dopamine / metabolism
Dopamine Agents / toxicity*
Guinea Pigs
Homovanillic Acid / metabolism
Neostriatum / enzymology*
Organ Culture Techniques
Tyrosine 3-Monooxygenase / metabolism
Uric Acid / metabolism
Reg. No./Substance:
0/Amino Acids; 0/Dopamine Agents; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 48134-75-4/1-Methyl-4-phenylpyridinium; 490-83-5/Dehydroascorbic Acid; 69-93-2/Uric Acid; EC 3-Monooxygenase

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