title: N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups.
abstract: OBJECTIVE
  Glutaric 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.
  
  
  METHODS
  Rat 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.
  
  
  RESULTS
  GA 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: 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.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Rodrigues
authors.forename: Mauren A
authors.initials: MA
authors.lastname: Souza
authors.forename: Danieli V
authors.initials: DV
authors.lastname: Magni
authors.forename: Ana Paula O
authors.initials: AP
authors.lastname: Ferreira
authors.forename: Bibiana C
authors.initials: BC
authors.lastname: Mota
authors.forename: Andreia M
authors.initials: AM
authors.lastname: Cardoso
authors.forename: Mariana
authors.initials: M
authors.lastname: Paim
authors.forename: Léder L
authors.initials: LL
authors.lastname: Xavier
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Maria Rosa C
authors.initials: MR
authors.lastname: Schetinger
authors.forename: Jaderson C
authors.initials: JC
authors.lastname: Da Costa
authors.forename: Luiz Fernando F
authors.initials: LF
authors.lastname: Royes
authors.forename: Michele R
authors.initials: MR
authors.lastname: Fighera
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D005977:Glutarates / Q000009:adverse effects* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005977:Glutarates; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000254:Sodium-Potassium-Exchanging ATPase; C035736:glutaric acid; D000111:Acetylcysteine