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

• Published in: Metabolic brain disease Vol. 24; no. 2; pp. 283 - 298
• Main Authors: Pederzolli, Carolina Didonet, Rockenbach, Francieli Juliana, Zanin, Fernanda Rech, Henn, Nicoli Taiana, Romagna, Eline Coan, Sgaravatti, Ângela M, Wyse, Angela T. S, Wannmacher, Clóvis M. D, Wajner, Moacir, de Mattos Dutra, Ângela, Dutra-Filho, Carlos S
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.06.2009; Springer US; Springer Nature B.V
• Subjects: Animals; Antioxidants - metabolism; Aspartic Acid - administration & dosage; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Aspartic Acid - toxicity; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain Damage, Chronic - etiology; Brain Damage, Chronic - metabolism; Canavan Disease - complications; Canavan Disease - metabolism; Catalase - drug effects; Catalase - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dipeptides - administration & dosage; Dipeptides - metabolism; Dipeptides - toxicity; Disease Models, Animal; Glucosephosphate Dehydrogenase - drug effects; Glucosephosphate Dehydrogenase - metabolism; Glutathione Peroxidase - drug effects; Glutathione Peroxidase - metabolism; Injections, Intraventricular; Lipid Peroxidation; Male; Metabolic Diseases; Neurology; Neuropeptides - administration & dosage; Neuropeptides - metabolism; Neuropeptides - toxicity; Neurosciences; Neurotoxins - administration & dosage; Neurotoxins - metabolism; Neurotoxins - toxicity; Oncology; Original Paper; Oxidation-Reduction; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Wistar; N-acetylaspartylglutamic acid; Canavan Disease; Oxidative stress; N-acetylaspartic acid; Aspartoacylase deficiency; Rat brain
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-009-9137-6

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.