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 m>in vivom>. 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 m>substantia nigram> and m>striatumm> 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 m>in vitrom> 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 m>substantia nigram> and m>striatumm> of vitamin A-treated rats were more sensitive to H₂O₂ than control mitochondria as assessed through the m>in vitrom> assay. Overall, these data may be useful to explain how vitamin A elicits neurotoxic effects chronically.