Diminished concentrations of ganglioside N-acetylneuraminic acid (G-NeuAc) in cerebellum of young rats receiving chronic administration of methylmalonic acid

Wajner, Moaçir; Brites, Eneida Carolina; Dutra, Janice Coelho; Buchalter, M.S; Pons, A.; Pires, Ricardo Flores; Wannmacher, Lenita; Júnior, A. R. P. Vieira; Trindade, Vera Maria Treis; Wannmacher, Clóvis Milton Duval

doi:10.1016/0022-510x(88)90159-1

Cited by 19 publications

(9 citation statements)

References 11 publications

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“…In addition, by administering proline (Pro) in doses varying as a function of the age and weight of the animals, we achieved proline plasma levels ten times those of non-treated animals, and similar to those found in patients affected by type II hyperprolinaemia (McKusick 2395100) (Moreira et al 1989). By using these chemicallyinduced models, learning/memory deficits and biochemical alterations were observed in brain of rats (Wajner et al 1988;Moreira et al 1989;Scriver et al 1989;Dutra et al 1991a, b).…”

Section: *Correspondencesupporting

confidence: 73%

Diminished concentration of the NF‐H subunit of neurofilaments in cerebral cortex of rats chronically treated with proline, methylmalonate and phenylalanine plus α‐methylphenylalanine

Rubin¹,

Wannmacher²,

Valente³

et al. 1991

J of Inher Metab Disea

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Wistar rats from the same litter were randomly divided into four groups and received subcutaneously from the 6th to 28th day post partum one of the following drugs: L-proline, methylmalonate, L-phenylalanine plus alpha-methylphenylalanine, or equivalent volumes of 0.9% (w/v) saline (controls). On day 30, the animals were killed, the brain was removed and the cerebral cortex and cerebellum was immediately dissected. Total intermediate filament fraction (IF) was obtained from cerebral cortex and cerebellum by using a high-salt phosphate-buffered solution supplemented by 1% Triton X-100. The pellet contained the bulk of the IF proteins. Following SDS-polyacrylamide gel electrophoresis, these proteins were identified as the 200, 150 and 68 kD subunits of neurofilaments (NF-H, NF-M and NF-L, respectively), the 66 kDa associated protein, the 57 kDa intermediate filament-like protein and the 52 kDa glial fibrillary acidic protein (GFAP). They were further scanned through densitometry from enriched fractions of controls and of animals treated with the various drugs in order to determine the effects of the treatments on their concentration. Our results showed that the concentration of IF protein in cerebellum was not affected by the treatments, whereas chronic administration of all drugs significantly decreased NF-H subunit concentration in rat cerebral cortex.

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Section: *Correspondencesupporting

confidence: 73%

Diminished concentration of the NF‐H subunit of neurofilaments in cerebral cortex of rats chronically treated with proline, methylmalonate and phenylalanine plus α‐methylphenylalanine

Rubin¹,

Wannmacher²,

Valente³

et al. 1991

J of Inher Metab Disea

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“…Those who survive present with a variable degree of physical and mental retardation (Rosenberg and Fenton 1989).Various metabolic effects have been attributed to MMA and methylmalonyl-CoA. We have previously found important effects of MMA on brain metabolism (Wajner et al 1982(Wajner et al , 1988Dutra et al 1989Dutra et al , 1991.…”

mentioning

confidence: 99%

Inhibition of succinate dehydrogenase and β‐hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats

Dutra

Dutra-Filho

Cardozo

et al. 1992

J of Inher Metab Disea

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The effects of methylmalonate (MMA) on succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase (HBDH) activities in brain and liver of 15-day-old rats were studied. The apparent Km of SDH for succinate was 0.45 mmol/L in brain and 0.34 mmol/L in liver. MMA inhibited the enzyme activity in both tissues with Ki values of 4.5 mmol/L and 2.3 mmol/L in brain and liver, respectively, and the inhibition was of the reversible competitive type. The calculated Km for HBDH with beta-hydroxybutyrate as substrate was 1.26 mmol/L in brain and 0.36 mmol/L in liver. MMA inhibited the enzyme with a Ki value of 0.015 mmol/L in brain and 0.275 mmol/L in liver. These results are probably relevant to our understanding of cerebral metabolism in methylmalonic acidaemic children, especially during ketoacidotic and hypoglycaemic crises, and may be related to the pathogenesis of cerebral dysfunction of methylmalonic acidaemia.

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“…Some studies have evaluated changes on lipid membranes caused by experimental CNS damages. In general, models of malnutrition (Morgan and Naismith, 1982; Trindade et al, 1992), neonatal hypoxia–ischemia (Qi and Xue, 1991; Ramirez et al, 2003); malonic and propionic acidemias (Wajner et al, 1988; Brusque et al, 1998; Trindade et al, 2002) and neurodegeneration as Creutzfield‐Jakob disease (Ohtani et al, 1996) determined lipid loss in the membrane of neural structures. Recently, we demonstrated a reduction of gangliosides, phospholipids and cholesterol contents in cerebral cortex of rats caused by chronic hypermethioninemia model (Stefanello et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic proline administration on lipid contents of rat brain

Vianna

Delwing

Kurek

et al. 2008

Intl J of Devlp Neuroscience

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In the present work we investigated the effects of chronic proline administration on ganglioside, cholesterol and phospholipid total contents, as well as on ganglioside profile in cerebral cortex, hippocampus, hypothalamus and cerebellum of rats. We also evaluated the ganglioside content and profile in detergent-soluble and resistant microdomains isolated from synaptic membranes obtained from cerebral cortex. Proline solution (hyperprolinemic) or saline (control) were subcutaneously administered to rats from 6th to 28th post-natal day, according to body weight. Twelve hours after the last injection, the animals were sacrificed by decapitation without anaesthesia. Brain structures were homogenized with chloroform:methanol for lipid extraction. Synaptic membranes were obtained by differential centrifugation and detergent-soluble and resistant microdomains were isolated by cold Triton X-100 treatment. Results showed that rats subjected to chronic proline treatment presented a significant increase of ganglioside content in cortex and hippocampus, while this membrane lipid content was not altered in hypothalamus and cerebellum. Besides, phospholipid and cholesterol contents were not modified in all structures studied. On the other hand, ganglioside content decreased in detergent-soluble and resistant microdomains isolated from synaptic membrane obtained from hyperprolinemic cortex. Although ganglioside profiles were apparently not modified, the individual absolute quantities were altered in cortex and hippocampus total lipid extract and membrane microdomains. Our findings suggest that chronic proline treatment affects in a distinct manner different cerebral regions concerning the lipid composition of the cell membranes, reflecting on its distribution in the cortex membrane microdomains. Among these phenomena consequences, distinct modulations in synaptic transmission may be suggested which might contribute to the impairment in cognition and/or other neurological dysfunctions found in hyperprolinemia type II patients.

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Diminished concentrations of ganglioside N-acetylneuraminic acid (G-NeuAc) in cerebellum of young rats receiving chronic administration of methylmalonic acid

Cited by 19 publications

References 11 publications

Diminished concentration of the NF‐H subunit of neurofilaments in cerebral cortex of rats chronically treated with proline, methylmalonate and phenylalanine plus α‐methylphenylalanine

Diminished concentration of the NF‐H subunit of neurofilaments in cerebral cortex of rats chronically treated with proline, methylmalonate and phenylalanine plus α‐methylphenylalanine

Inhibition of succinate dehydrogenase and β‐hydroxybutyrate dehydrogenase activities by methylmalonate in brain and liver of developing rats

Effects of chronic proline administration on lipid contents of rat brain

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