Farris Sean P, Tiwari Gayatri R, Ponomareva Olga, Lopez Marcelo F, Mayfield R Dayne, Becker Howard C
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15206, USA.
Brain Sci. 2020 May 2;10(5):275. doi: 10.3390/brainsci10050275.
Chronic stress is a known contributing factor to the development of drug and alcohol addiction. Animal models have previously shown that repeated forced swim stress promotes escalated alcohol consumption in dependent animals. To investigate the underlying molecular adaptations associated with stress and chronic alcohol exposure, RNA-sequencing and bioinformatics analyses were conducted on the prefrontal cortex (CTX) of male C57BL/6J mice that were behaviorally tested for either non-dependent alcohol consumption (CTL), chronic intermittent ethanol (CIE) vapor dependent alcohol consumption, repeated bouts of forced swim stress alone (FSS), and chronic intermittent ethanol with forced swim stress (CIE + FSS). Brain tissue from each group was collected at 0-h, 72-h, and 168-h following the final test to determine long-lasting molecular changes associated with maladaptive behavior. Our results demonstrate unique temporal patterns and persistent changes in coordinately regulated gene expression systems with respect to the tested behavioral group. For example, increased expression of genes involved in "transmitter-gated ion channel activity" was only determined for CIE + FSS. Overall, our results provide a summary of transcriptomic adaptations across time within the CTX that are relevant to understanding the neurobiology of chronic alcohol exposure and stress.
慢性应激是已知导致药物和酒精成瘾的一个因素。动物模型先前已表明，反复强迫游泳应激会促使依赖动物的酒精摄入量增加。为了研究与应激和慢性酒精暴露相关的潜在分子适应性变化，对雄性C57BL/6J小鼠的前额叶皮质（CTX）进行了RNA测序和生物信息学分析，这些小鼠在行为上被测试为非依赖性酒精摄入（CTL）、慢性间歇性乙醇（CIE）蒸气依赖性酒精摄入、单独反复进行强迫游泳应激（FSS）以及慢性间歇性乙醇合并强迫游泳应激（CIE + FSS）。在最后一次测试后的0小时、72小时和168小时收集每组的脑组织，以确定与适应不良行为相关的长期分子变化。我们的结果表明，在所测试的行为组中，协调调节的基因表达系统存在独特的时间模式和持续变化。例如，仅在CIE + FSS组中确定了参与“递质门控离子通道活性”的基因表达增加。总体而言，我们的结果总结了CTX内随时间变化的转录组适应性变化，这对于理解慢性酒精暴露和应激的神经生物学具有重要意义。
