• Fernanda S Rodrigues, Mauren A Souza, Danieli V Magni, Ana Paula O Ferreira, Bibiana C Mota, Andreia M Cardoso, Mariana Paim, Léder L Xavier, Juliano Ferreira, Maria Rosa C Schetinger, Jaderson C Da Costa, Luiz Fernando F Royes, and Michele R Fighera.
• Centro de Ciências da Saúde, Departamento de Neuropsiquiatria, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brasil ; Centro de Ciências Naturais e Exatas, Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brasil ; Centro de Educação Física e Desportos, Departamento de Métodos e Técnicas Desportivas, Laboratório de Bioquímica do Exercício (BIOEX), Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brasil.
• Plos One. 2013 Jan 1;8(10):e78332.

Background And AimsGlutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers.MethodsRat pups were injected with GA (5 umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). LPS (2 mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed.ResultsGA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers.ConclusionsThese results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible adjuvant therapy in treatment of children with GA-I.

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