Document Detail

Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuraminic acid concentration in cerebrum of young rats.
MedLine Citation:
PMID:  11175498     Owner:  NLM     Status:  MEDLINE    
Levels of methylmalonic acid (MMA) comparable to those of human methylmalonic acidemia were achieved in blood (2-2.5 mmol/l) and brain (1.35 umol/g) of rats by administering buffered MMA, pH 7.4, subcutaneously twice a day from the 5th to the 28th day of life. MMA doses ranged from 0.76 to 1.67 umol/g as a function of animal age. Control rats were treated with saline in the same volumes. The animals were sacrificed by decapitation on the 28th day of age. Blood was taken and the brain was rapidly removed. Medulla, pons, the olfactory lobes and cerebellum were discarded and the rest of the brain ("cerebrum") was isolated. Body and "cerebrum" weight were measured, as well as the cholesterol and triglyceride concentrations in blood and the content of myelin, total lipids, and the concentrations of the lipid fractions (cholesterol, glycerolipids, phospholipids and ganglioside N-acetylneuraminic acid (ganglioside-NANA)) in the "cerebrum". Chronic MMA administration had no effect on body or "cerebrum" weight, suggesting that the metabolites per se neither affect the appetite of the rats nor cause malnutrition. In contrast, MMA caused a significant reduction of plasma triglycerides, but not of plasma cholesterol levels. A significant diminution of myelin content and of ganglioside-NANA concentration was also observed in the "cerebrum". We propose that the reduction of myelin content and ganglioside-NANA caused by MMA may be related to the delayed myelination/cerebral atrophy and neurological dysfunction found in methylmalonic acidemic children.
A Brusque; L Rotta; L F Pettenuzzo; D Junqueira; C V Schwarzbold; A T Wyse; C M Wannmacher; C S Dutra-Filho; M Wajner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.]     Volume:  34     ISSN:  0100-879X     ISO Abbreviation:  Braz. J. Med. Biol. Res.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-05-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8112917     Medline TA:  Braz J Med Biol Res     Country:  Brazil    
Other Details:
Languages:  eng     Pagination:  227-31     Citation Subset:  IM    
Departamento de Bioquímica, Instituto das Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
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MeSH Terms
Animals, Newborn
Brain Chemistry*
Cholesterol / metabolism
Gangliosides / metabolism*
Lipid Metabolism*
Methylmalonic Acid / administration & dosage*,  pharmacology
Myelin Sheath / drug effects*
Phospholipids / metabolism
Rats, Wistar
Sialic Acids / metabolism*
Triglycerides / metabolism
Reg. No./Substance:
0/Gangliosides; 0/Phospholipids; 0/Sialic Acids; 0/Triglycerides; 516-05-2/Methylmalonic Acid; 57-88-5/Cholesterol

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