Vizuete Adriana Fernanda Kuckartz, Mussulini Ben Hur, Zenki Kamila Cagliari, Baggio Suelen, Pasqualotto Amanda, Rosemberg Denis Broock, Bogo Maurício Reis, de Oliveira Diogo Lösch, Rico Eduardo Pacheco
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos 2600-Anexo, 90035-003, Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, 97105-900, Santa Maria, RS, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA, 70458, USA.
Neurotoxicology. 2022 Jan;88:57-64. doi: 10.1016/j.neuro.2021.10.014. Epub 2021 Oct 30.
High ethanol (EtOH) consumption is a serious condition that induces tremors, alcoholic psychosis, and delirium, being considered a public health problem worldwide. Prolonged EtOH exposure promotes neurodegeneration, affecting several neurotransmitter systems and transduction signaling pathways. Glutamate is the major excitatory amino acid in the central nervous system (CNS) and the extracellular glutamatergic tonus is controlled by glutamate transporters mostly located in astrocytes. Here, we explore the effects of prolonged EtOH exposure on the glutamatergic uptake system and its relationship with astroglial markers (GFAP and S100B), neuroinflammation (IL-1β and TNF-α), and brain derived neurotrophic factor (BDNF) levels in the CNS of adult zebrafish. Animals were exposed to 0.5% EtOH for 7, 14, and 28 days continuously. Glutamate uptake was significantly decreased after 7 and 14 days of EtOH exposure, returning to baseline levels after 28 days of exposure. No alterations were observed in crucial enzymatic activities linked to glutamate uptake, like Na,K-ATPase or glutamine synthetase. Prolonged EtOH exposure increased GFAP, S100B, and TNF-α levels after 14 days. Additionally, increased BDNF mRNA levels were observed after 14 and 28 days of EtOH exposure, while BDNF protein levels increased only after 28 days. Collectively, our data show markedly brain astroglial, neuroinflammatory and neurotrofic responses after an initial impairment of glutamate uptake following prolonged EtOH exposure. This neuroplasticity event could play a key role in the modulatory effect of EtOH on glutamate uptake after 28 days of continuous exposure.
高乙醇（EtOH）摄入量是一种严重的情况，会引发震颤、酒精性精神病和谵妄，被视为全球范围内的一个公共卫生问题。长期接触EtOH会促进神经退行性变，影响多个神经递质系统和转导信号通路。谷氨酸是中枢神经系统（CNS）中的主要兴奋性氨基酸，细胞外谷氨酸能张力由主要位于星形胶质细胞中的谷氨酸转运体控制。在此，我们探讨了长期接触EtOH对谷氨酸能摄取系统的影响及其与成年斑马鱼CNS中星形胶质细胞标志物（GFAP和S100B）、神经炎症（IL-1β和TNF-α）以及脑源性神经营养因子（BDNF）水平的关系。动物连续7天、14天和28天暴露于0.5%的EtOH中。EtOH暴露7天和14天后，谷氨酸摄取显著降低，暴露28天后恢复到基线水平。与谷氨酸摄取相关的关键酶活性，如钠钾ATP酶或谷氨酰胺合成酶，未观察到改变。长期EtOH暴露14天后，GFAP、S
