Total and Mitochondrial Nitrosative Stress, Decreased Brain-Derived Neurotrophic Factor (BDNF) Levels and Glutamate Uptake, and Evidence of Endoplasmic Reticulum Stress in the Hippocampus of Vitamin A-Treated Rats
Total and Mitochondrial Nitrosative Stress, Decreased Brain-Derived Neurotrophic Factor (BDNF) Levels and Glutamate Uptake, and Evidence of Endoplasmic Reticulum Stress in the Hippocampus of Vitamin A-Treated Rats
复制标题
DOI：
10.1007/s11064-010-0372-3
复制
发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Fonseca Moreira, Jose Claudio
中科院分区：
文献类型：
--
作者：
de Oliveira, Marcos Roberto;da Rocha, Ricardo Fagundes;Fonseca Moreira, Jose Claudio
维生素A补充剂引起了公共卫生研究人员的关注，因为它能够降低生活质量，从急性毒理学效应到增加维生素补充剂使用者的死亡率。例如，它描述了接受长期维生素A治疗的患者的认知能力下降（即易怒，焦虑和抑郁），如癌症治疗中发生的那样。然而，维生素A影响哺乳动物认知的机制尚未完全了解。然后，我们进行了目前的工作，以研究临床剂量（1，000 - 9，000 IU/kg/天（-1））补充维生素A 28天对大鼠海马亚硝化应激水平（总的和线粒体），生物能量学状态，脑源性神经营养因子（BDNF），α-和β-突触核蛋白，BiP和多巴胺受体2（D2受体）含量以及谷氨酸摄取的影响。我们观察到呼吸链功能的线粒体损伤：复合物I-III增加，但复合物IV酶活性降低。此外，在维生素A治疗的大鼠中观察到BDNF水平降低。目前的数据表明，至少部分地，线粒体功能障碍和BDNF和D2受体水平降低，以及谷氨酸摄取减少可能在先前报道的与维生素A补充相关的认知障碍背后的机制中发挥重要作用。
Vitamin A supplementation has caused concern among public health researchers due to its ability in decreasing life quality from acute toxicological effects to increasing mortality rates among vitamin supplement users. For example, it was described cognitive decline (i.e. irritability, anxiety, and depression) in patients subjected to long-term vitamin A therapy, as occurs in cancer treatment. However, the mechanism by which vitamin A affects mammalian cognition is not completely understood. Then, we performed the present work to investigate the effects of vitamin A supplementation at clinical doses (1,000-9,000 IU/kg day(-1)) for 28 days on rat hippocampal nitrosative stress levels (both total and mitochondrial), bioenergetics states, brain-derived neurotrophic factor (BDNF), alpha- and beta-synucleins, BiP and dopamine receptor 2 (D2 receptor) contents, and glutamate uptake. We observed mitochondrial impairment regarding respiratory chain function: increased complex I-III, but decreased complex IV enzyme activity. Also, decreased BDNF levels were observed in vitamin A-treated rats. The present data demonstrates, at least in part, that mitochondrial dysfunction and decreased BDNF and D2 receptors levels, as well as decreased glutamate uptake may take an important role in the mechanism behind the previously reported cognitive disturbances associated to vitamin A supplementation.