Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats.

[canavan disease]

N-acetylaspartic acid (NAA ) is the biochemical hallmark of Canavan Disease , an inherited metabolic disease caused by deficiency of aspartoacylase activity . NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG ), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD . This neurodegenerative disorder is clinically characterized by severe mental retardation , hypotonia and macrocephaly , and generalized tonic and clonic type seizures . Considering that the mechanisms of brain damage in this disease remain not fully understood , in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30 -day -old rats . NAA significantly reduced total radical-trapping antioxidant potential , catalase and glucose 6 -phosphate dehydrogenase activities , whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced . Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA . In contrast , NAAG did not alter any of the oxidative stress parameters tested . Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins , which could be involved in the neurotoxicity of NAA accumulation in CD patients .