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Propionic acid induces convulsions and protein carbonylation in rats

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
408
Issue
2
Identifiers
DOI: 10.1016/j.neulet.2006.08.075
Keywords
  • Propionic Acidemia
  • Seizure
  • Nmda Receptor
  • Neurotoxicity
  • Oxidative Stress
  • Protein Carbonyl
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Propionic acid (PA) accumulates in patients with propionic acidemia, an inherited metabolic disorder caused by the deficiency of propionyl-CoA carboxylase activity that is clinically characterized by neurological dysfunction, including seizures. However, it is not known whether PA causes seizures in experimental animals. In the current study, we investigated whether intrastriatal injection of PA (0.6–6 μmol) causes seizures and alters protein carbonyl content in the striatum of adult rats. The injection of PA caused the appearance of seizures and increased protein carbonyl content in injected and noninjected striata. PA-induced seizures and increased protein carbonylation in the striatum were prevented by the injection of MK-801 (3 nmol/0.5 μL). Our results suggest that PA causes seizures and oxidative damage by NMDA receptor-mediated mechanisms. The involvement of NMDA receptors in the pathogenesis of propionic acidemia is suggested.

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