The effects of vitamin A supplementation for 3 months on adult rat nigrostriatal axis: Increased monoamine oxidase enzyme activity, mitochondrial redox dysfunction, increased 尾-amyloid_1-40 peptide and TNF-伪 contents, and susceptibility of mit

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• 作者：Marcos Roberto de Oliveira ; ^{mrobioq@gmail.com} ; ^{mrobioq@yahoo.com.br} ; Ricardo Fagundes da Rocha ; Matheus Augusto de Bittencourt Pasquali ; José ; Clá ; udio Fonseca Moreira
• 关键词：Vitamin A ; Substantia nigra ; Striatum ; Monoamine oxidase ; 3-Nitrotyrosine
• 刊名：Brain Research Bulletin
• 出版年：2012
• 期刊代码：9_03619230
• 类别：neu
• 出版时间：10 March, 2012
• 卷：87
• 期：4-5
• 页码：432-444
• 文件大小：648 K

摘要

Even though vitamin A has been viewed as an antioxidant molecule, recent findings demonstrate that such vitamin elicits pro-oxidant effects in vivo. Moreover, vitamin A supplements utilization may increase mortality rates among healthy subjects. However, the mechanism by which vitamin A elicits such effects remains to be better analyzed. In this regard, we investigated here the consequences of vitamin A supplementation at 500, 1000, or 2500 IU/kg day^鈭? for 3 months on adult rat substantia nigra and striatum total and mitochondrial redox state (both oxidative and nitrosative stress markers), electron transfer chain activity, monoamine oxidase (MAO) enzyme activity, endoplasmic reticulum stress marker (BiP), 伪- and 尾-synucleins, 尾-amyloid peptide (1-40), dopamine D2 receptor (D2R), receptor for advanced glycation end products (RAGE), caspase-3 and caspase-8 enzyme activity and tumor necrosis factor-伪 (TNF-伪) levels. Also, nigrostriatal mitochondria were isolated and challenged with 50 渭M H₂O₂ in vitro after vitamin A supplementation and complexes I-III, II-III, and IV enzyme activity was recorded. We observed both total and mitochondrial oxidative and nitrosative stress, increased MAO enzyme activity, and increased levels of 伪-synuclein, 尾-amyloid peptide, RAGE, and TNF-伪, but decreased D2R in both rat brain areas. Furthermore, vitamin A supplementation induced a decrease in nigral, but not striatal, 尾-synuclein levels in this work. Moreover, mitochondria isolated from both substantia nigra and striatum of vitamin A-treated rats were more sensitive to H₂O₂ than control mitochondria as assessed through the in vitro assay. Overall, these data may be useful to explain how vitamin A elicits neurotoxic effects chronically.