Rajput Prabha, Jangra Ashok, Kwatra Mohit, Mishra Abhishek, Lahkar Mangala
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India.
KIET School of Pharmacy, Krishna Institute of Engineering and Technology, Ghaziabad, Uttar Pradesh, India.
Biomed Pharmacother. 2017 Jul;91:457-466. doi: 10.1016/j.biopha.2017.04.077. Epub 2017 May 4.
Stressful events and alcohol abuse are the cumbersome situations which can synergistically predispose the negative effects on the brain. Oxidative stress generated by chronic immobilization and alcohol consumption cause severe neurotoxicity in the hippocampus region that ultimately leads to cognitive dysfunction. In the current study, we have investigated the involvement of NF-κB/Nrf/HO-1 transduction pathway in stress and alcohol exposed animals. Male Swiss albino mice were given alcohol (ALC) (15% v/v) or restraint stress (RS) or both (RS for 6h per day) up to 28days. We found increased ALC consumption in the ALC+RS group as compared to the ALC group. Morris water maze (MWM) test and novel object recognition test (NORT) revealed the spatial and recognition memory impairment in RS and ALC+RS group. ALC+RS group showed more profound oxidative stress and augmentation of pro-inflammatory cytokine (IL-1β) as compared to RS or ALC group alone. Melatonin (20mg/kg, p.o) treatment for 14days significantly prevented the raised oxidative stress, release of IL-1β, GSH depletion and augmentation of AChE activity in the hippocampus. Moreover, semi-quantitative reverse transcriptase PCR results showed that combined exposure of ALC and RS leads to over-activation of NF-κB transduction inflammatory pathway and down-regulation of the Nrf2/HO-1 axis which was significantly ameliorated by the melatonin treatment. In conclusion, our results indicated that ALC+RS exerted the deleterious effects on the hippocampus which were alleviated by the melatonin treatment.
应激事件和酒精滥用是可能协同引发对大脑负面影响的棘手情况。慢性固定和酒精摄入所产生的氧化应激会在海马体区域导致严重的神经毒性，最终引发认知功能障碍。在本研究中，我们调查了NF-κB/Nrf/HO-1转导通路在应激和酒精暴露动物中的作用。雄性瑞士白化小鼠接受酒精（ALC）（15% v/v）或束缚应激（RS）或两者同时处理（RS每天6小时），持续28天。我们发现与ALC组相比，ALC+RS组的酒精摄入量增加。莫里斯水迷宫（MWM）试验和新物体识别试验（NORT）显示RS组和ALC+RS组存在空间和识别记忆损伤。与单独的RS组或ALC组相比，ALC+RS组表现出更严重的氧化应激和促炎细胞因子（IL-1β）增加。褪黑素（20mg/kg，口服）治疗14天可显著预防海马体中氧化应激增加、IL-1β释放、谷胱甘肽耗竭和乙酰胆碱酯酶活性增强。此外，半定量逆转录酶PCR结果表明，ALC和RS联合暴露会导致NF-κB转导炎症通路过度激活以及Nrf2/HO-1轴下调，而褪黑素治疗可显著改善这种情况。总之，我们的结果表明ALC+RS对海马体产生了有害影响，而褪黑素治疗可减轻这些影响。
