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Neurochemical Research

, Volume 30, Issue 9, pp 1123–1131 | Cite as

Glutaric Acid Administration Impairs Energy Metabolism in Midbrain and Skeletal Muscle of Young Rats

  • Gustavo da C. Ferreira
  • Carolina M. Viegas
  • Patrícia F. Schuck
  • Anelise Tonin
  • César A. J. Ribeiro
  • Daniella de M. Coelho
  • Teresa Dalla-Costa
  • Alexandra Latini
  • Ângela T. S. Wyse
  • Clovis M. D. Wannmacher
  • Carmen R. Vargas
  • Moacir Wajner
Article

Abstract

A genetic mice model of glutaric acidemia type I (GAI) has recently been developed, however affected animals do not develop the striatal damage characteristic of patients with this disorder. Therefore, the initial aim of the present work was to induce high glutaric acid (GA) concentrations in rat brain similar to those found in GAI patients through subcutaneous injection of GA. High brain GA concentrations (up to 0.60 μmol/g ≅ 0.60mM) were achieved by a single subcutaneous injection of saline-buffered GA (5 μmol/g body weight) to Wistar rats of 7–22 days of life. GA brain levels were about 10-fold lower than in plasma and 5-fold lower than in skeletal and cardiac muscles, indicating that the permeability of the blood brain barrier to GA is low. We also aimed to use this model to investigate neurochemical parameters in the animals. Thus, we evaluated the effect of this model on energy metabolism parameters in midbrain, in which the striatum is localized, as well as in peripheral tissues (skeletal and cardiac muscles) of 22-day-old rats. Control rats were treated with saline in the same volumes. We verified that CO2 production from glucose was not altered in midbrain of rats treated with GA, indicating a normal functioning of the tricarboxylic acid cycle. Creatine kinase activity was also not changed in midbrain, skeletal and cardiac muscles. In contrast, complex I–III activity of the respiratory chain was inhibited in midbrain (25%), while complexes I–III (25%) and II–III (15%) activities were reduced in skeletal muscle, with no alterations found in cardiac muscle. These data indicate that GA administration moderately impairs cellular energy metabolism in midbrain and skeletal muscle of young rats.

Key words

CO2 production and energy metabolism creatine kinase  glutaric acid respiratory chain complexes 

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Gustavo da C. Ferreira
    • 1
  • Carolina M. Viegas
    • 1
  • Patrícia F. Schuck
    • 1
  • Anelise Tonin
    • 1
  • César A. J. Ribeiro
    • 1
  • Daniella de M. Coelho
    • 2
  • Teresa Dalla-Costa
    • 3
  • Alexandra Latini
    • 1
  • Ângela T. S. Wyse
    • 1
  • Clovis M. D. Wannmacher
    • 1
  • Carmen R. Vargas
    • 1
    • 2
    • 3
  • Moacir Wajner
    • 1
    • 2
    • 4
  1. 1.Departamento de BioquímicaICBS, Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Serviço de Genética MédicaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Faculdade de FarmáciaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Universidade Luterana do BrasilCanoasBrazil

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