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Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuramic acid concentration in cerebrum of young rats

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Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuramic acid concentration in cerebrum of young rats

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Título Chronic postnatal administration of methylmalonic acid provokes a decrease of myelin content and ganglioside N-acetylneuramic acid concentration in cerebrum of young rats
Autor Brusque, Ana Maria
Rotta, Liane Nanci
Pettenuzzo, Letícia Ferreira
Junqueira, Debora
Schwarzbold, Carolina Vargas
Wyse, Angela Terezinha de Souza
Wannmacher, Clovis Milton Duval
Dutra Filho, Carlos Severo
Wajner, Moacir
Abstract 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 µmol/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 µmol/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.
Contido em Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas. Ribeirão Preto, SP. Vol. 34, no. 2 (Feb. 2001), p. 227-231
Assunto Bioquímica
[en] Glycerides
[en] Lipids
[en] Methylmalonic acid
[en] Methylmalonic acidemia
[en] Myelin
[en] Rat brain
Origem Nacional
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/21136
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