Programa de Pós-graduação em Neurociências, Laboratório de Neurociências Comportamental e Molecular, LaNeC, Universidade Federal de Minas Gerais, Belo Horizonte 31270-010, Brazil.
Escola de Medicina Veterinária, Laboratório Oficial Central do Ministério da Agricultura Pecuária e Abastecimento - AQUACEN, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
Neuroscience. 2018 Aug 10;385:181-197. doi: 10.1016/j.neuroscience.2018.06.003. Epub 2018 Jun 9.
Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. Following 15 days of recovery, all rats were submitted to the spatial cognitive tasks in the Morris Water Maze (MWM). The results show that the PTD rats exhibited deficits during the learning process, which was reverted by repeated training. However, despite the spatial cognitive recovery, some protein changes were not reversible. The proteomic analysis, using label-free quantification, revealed deregulation of 183 thalamic proteins. Using bioinformatic tools, these proteins were categorized according to Gene Ontology functional annotation and metabolic pathways. We show that a severe TD affects proteins involved in different biological processes, such as, oxidative stress, neurotransmitter synthesis and synaptic vesicle cycle. These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult.
硫胺素缺乏症 (TD) 已被用作啮齿动物的实验模型，以研究神经退行性变的分子机制及其与行为变化的关系。本研究的目的是研究吡哆醇诱导的硫胺素缺乏症 (PTD) 对成年雄性大鼠空间认知表现的影响，并揭示严重 TD 发作引起的丘脑蛋白质组改变。在出现抽搐和/或翻正反射丧失等神经症状后，中断 TD 治疗。经过 15 天的恢复期，所有大鼠都接受了 Morris 水迷宫 (MWM) 中的空间认知任务。结果表明，PTD 大鼠在学习过程中表现出缺陷，经过反复训练得到恢复。然而，尽管空间认知得到恢复，但一些蛋白质变化仍不可逆转。使用无标记定量的蛋白质组学分析显示，183 个丘脑蛋白发生了下调。通过生物信息学工具，根据基因本体功能注释和代谢途径对这些蛋白质进行了分类。我们表明，严重的 TD 会影响涉及不同生物学过程的蛋白质，如氧化应激、神经递质合成和突触小泡循环。这些可以解释 TD 引起的神经递质释放变化的结果，这是我们小组和其他作者之前观察到的。这些发现揭示了可能参与 TD 诱导的神经退行性变过程的关键蛋白质和代谢途径的作用。这些蛋白质代表了未来研究的相关分子靶点，也关注 TD 损伤对某些大脑区域选择性易感性的分子基础。
