Cruz Catarina, Meireles Manuela, Silva Susana M
Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal; Center for Health Tecnology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450, Porto, Portugal.
Center for Health Tecnology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450, Porto, Portugal; School of Health, University of Algarve, Rua Eng. José Campos Coroa, 8000-510, Faro, Portugal.
Neurotoxicology. 2017 May;60:107-115. doi: 10.1016/j.neuro.2017.04.005. Epub 2017 Apr 10.
Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol.
神经炎症与多种疾病的发病机制有关。小胶质细胞的激活会导致促炎介质的释放，并且小胶质细胞介导的神经炎症已被认为是酒精诱导的神经病理机制之一。本研究旨在探讨慢性乙醇暴露和长期戒断对海马结构中小胶质细胞激活和神经炎症的影响。雄性大鼠接受6个月的乙醇处理，随后有2个月的戒断期。应用体视学方法估计通过CD11b免疫组织化学检测到的海马结构中小胶质细胞和活化小胶质细胞的总数。通过qRT-PCR测量促炎细胞因子TNF-α、COX-2和IL-15的表达水平。酒精摄入与活化小胶质细胞总数的增加有关，但形态学评估表明小胶质细胞未表现出完全激活的表型。这些数据得到了功能证据的支持，因为慢性酒精摄入并未使TNF-α或COX-2的表达发生变化。IL-15是一种在星形胶质细胞和小胶质细胞激活时表达都会增加的细胞因子，其水平在慢性酒精处理后升高。重要的是，长期戒断并未逆转乙醇诱导的小胶质细胞部分激活。本研究表明，慢性酒精暴露诱导出一种与部分激活一致的小胶质细胞表型，而海马结构中神经炎症的经典细胞因子标志物并未显著增加。此外，长期戒酒不足以改变乙醇诱导的小胶质细胞部分激活表型。
