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Impact of intermittent voluntary ethanol consumption during adolescence on the expression of endocannabinoid system and neuroinflammatory mediators
European Neuropsychopharmacology ( IF 6.1 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.euroneuro.2020.01.012 L Sanchez-Marin 1 , A L Gavito 1 , J Decara 1 , A Pastor 2 , E Castilla-Ortega 1 , J Suarez 1 , R de la Torre 2 , F J Pavon 3 , F Rodriguez de Fonseca 1 , A Serrano 1
European Neuropsychopharmacology ( IF 6.1 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.euroneuro.2020.01.012 L Sanchez-Marin 1 , A L Gavito 1 , J Decara 1 , A Pastor 2 , E Castilla-Ortega 1 , J Suarez 1 , R de la Torre 2 , F J Pavon 3 , F Rodriguez de Fonseca 1 , A Serrano 1
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The adolescent brain displays high vulnerability to the deleterious effects of ethanol, including greater risk of developing alcohol use disorder later in life. Here, we characterized the gene expression of the endocannabinoid system (ECS) and relevant signaling systems associated with neuroinflammation and emotional behaviors in the brain of young adult control and ethanol-exposed (EtOH) rats. We measured mRNA levels of candidate genes using quantitative real time PCR in the medial prefrontal cortex (mPFC), amygdala and hippocampus. EtOH rats were generated by maintenance on an intermittent and voluntary ethanol consumption during adolescence using the two-bottle choice paradigm (4 days/week for 4 weeks) followed by 2 week-withdrawal, a time-point of withdrawal with no physical symptoms. Mean differences and effect sizes were calculated using t-test and Cohen's d values. In the mPFC and hippocampus, EtOH rats had significantly higher mRNA expression of endocannabinoid-signaling (mPFC: Ppara, Dagla, Daglb and Napepld; and hippocampus: Cnr2, Dagla and Mgll) and neuroinflammation-associated genes (mPFC: Gfap; and hippocampus: Aif1) than in controls. Moreover, EtOH rats had significantly higher mRNA expression of neuropeptide Y receptor genes (Npy1r, Npy2r and Npy5r) in the hippocampus. Finally, EtOH rats also displayed higher plasma endocannabinoid levels than controls. In conclusion, these results suggest that adolescent ethanol exposure can lead to long-term alterations in the gene expression of the ECS and other signaling systems involved in neuroinflammation and regulation of emotional behaviors in key brain areas for the development of addiction.
中文翻译：
青春期间歇性自愿饮酒对内源性大麻素系统和神经炎症介质表达的影响
青少年大脑对乙醇的有害影响非常脆弱，包括在以后的生活中患酒精使用障碍的风险更大。在这里，我们表征了内源性大麻素系统 (ECS) 的基因表达以及与年轻成人对照和乙醇暴露 (EtOH) 大鼠大脑中的神经炎症和情绪行为相关的相关信号系统。我们使用实时定量 PCR 在内侧前额叶皮层 (mPFC)、杏仁核和海马中测量了候选基因的 mRNA 水平。EtOH 大鼠是通过在青春期使用两瓶选择范式（4 天/周，持续 4 周）维持间歇性和自愿性乙醇消耗而产生的，然后停药 2 周，这是一个没有身体症状的停药时间点。使用 t 检验和 Cohen's d 值计算平均差异和效果大小。在 mPFC 和海马中，EtOH 大鼠的内源性大麻素信号（mPFC：Ppara、Dagla、Daglb 和 Napepld；和海马：Cnr2、Dagla 和 Mgll）和神经炎症相关基因（mPFC：Gfap；和海马： Aif1) 比在控件中。此外，EtOH 大鼠海马神经肽 Y 受体基因（Npy1r、Npy2r 和 Npy5r）的 mRNA 表达显着升高。最后，EtOH 大鼠的血浆内源性大麻素水平也高于对照组。综上所述，
更新日期：2020-04-01
中文翻译：
青春期间歇性自愿饮酒对内源性大麻素系统和神经炎症介质表达的影响
青少年大脑对乙醇的有害影响非常脆弱，包括在以后的生活中患酒精使用障碍的风险更大。在这里，我们表征了内源性大麻素系统 (ECS) 的基因表达以及与年轻成人对照和乙醇暴露 (EtOH) 大鼠大脑中的神经炎症和情绪行为相关的相关信号系统。我们使用实时定量 PCR 在内侧前额叶皮层 (mPFC)、杏仁核和海马中测量了候选基因的 mRNA 水平。EtOH 大鼠是通过在青春期使用两瓶选择范式（4 天/周，持续 4 周）维持间歇性和自愿性乙醇消耗而产生的，然后停药 2 周，这是一个没有身体症状的停药时间点。使用 t 检验和 Cohen's d 值计算平均差异和效果大小。在 mPFC 和海马中，EtOH 大鼠的内源性大麻素信号（mPFC：Ppara、Dagla、Daglb 和 Napepld；和海马：Cnr2、Dagla 和 Mgll）和神经炎症相关基因（mPFC：Gfap；和海马： Aif1) 比在控件中。此外，EtOH 大鼠海马神经肽 Y 受体基因（Npy1r、Npy2r 和 Npy5r）的 mRNA 表达显着升高。最后，EtOH 大鼠的血浆内源性大麻素水平也高于对照组。综上所述，
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