N-Acetylcysteine Prevents Spatial Memory Impairment Induced by Chronic Early Postnatal Glutaric Acid and Lipopolysaccharide in Rat Pups

被引:26
|
作者
Rodrigues, Fernanda S. [1 ,2 ,6 ]
Souza, Mauren A. [1 ,2 ,6 ]
Magni, Danieli V. [8 ]
Ferreira, Ana Paula O. [1 ,2 ,6 ]
Mota, Bibiana C. [1 ,2 ,6 ]
Cardoso, Andreia M. [2 ]
Paim, Mariana [5 ]
Xavier, Leder L. [5 ]
Ferreira, Juliano [2 ]
Schetinger, Maria Rosa C. [2 ]
Da Costa, Jaderson C. [3 ,4 ]
Royes, Luiz Fernando F. [2 ,6 ,7 ]
Fighera, Michele R. [1 ,2 ,6 ,7 ]
机构
[1] Univ Fed Santa Maria, Dept Neuropsiquiatria, Ctr Ciencias Saude, BR-97119900 Santa Maria, RS, Brazil
[2] Univ Fed Santa Maria, Ctr Ciencias Nat & Exatas, Programa Posgrad Ciencias Biol Bioquim Toxicol, BR-97119900 Santa Maria, RS, Brazil
[3] Pontificia Univ Catolica Rio Grande do Sul, Inst Pesquisas Biomed, Lab Neurociencias, Porto Alegre, RS, Brazil
[4] Pontificia Univ Catolica Rio Grande do Sul, Inst Cerebro, Porto Alegre, RS, Brazil
[5] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Dept Ciencias Fisiol, Porto Alegre, RS, Brazil
[6] Univ Fed Santa Maria, Lab Bioquim Exercicio BIOEX, Dept Metodos & Tecn Desportivas, Ctr Educ Fis & Desportos, BR-97119900 Santa Maria, RS, Brazil
[7] Univ Fed Santa Maria, Dept Fisiol & Farmacol, Programa Posgrad Farmacol, Ctr Ciencias Saude, BR-97119900 Santa Maria, RS, Brazil
[8] Univ Reg Integrada Alto Uruguai & Missoes, Santiago, RS, Brazil
来源
PLOS ONE | 2013年 / 8卷 / 10期
关键词
COA DEHYDROGENASE-DEFICIENCY; NITRIC-OXIDE SYNTHASES; NA+-K+-ATPASE; NA+; K+-ATPASE ACTIVITY; OXIDATIVE STRESS; ALZHEIMER-DISEASE; REDOX STATE; COGNITIVE DEFICITS; DORSAL-HIPPOCAMPUS; HYDROGEN-PEROXIDE;
D O I
10.1371/journal.pone.0078332
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background and Aims: 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 (5umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). LPS (2mg/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-alpha and IL-1 beta levels. The co-administration of these compounds potentiated the increase of IL-1 beta levels but not TNF-alpha 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.
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页数:18
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