tnf- α抑制剂对小鼠化学脑模型中焦虑和抑郁样行为的影响

M. Öz, N. Akaras
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引用次数: 1

摘要

化疗虽然提高了癌症患者的存活率,但也会产生认知功能恶化等严重的副作用,导致患者的生活水平下降。在我们的研究中,我们研究了阿达木单抗对甲氨蝶呤认知障碍小鼠焦虑和抑郁样行为的影响。在我们的研究中,甲氨蝶呤(40 mg kg-1)以单剂量腹腔注射,在小鼠体内建立化学脑模型。阿达木单抗(10mg kg-1)是一种tnf - α抑制剂,在甲氨蝶呤给药前1小时和5天给药两次。采用升高+迷宫法和开阔场法测定焦虑样行为,采用悬尾法测定抑郁样行为,并对海马组织进行组织病理学检查。甲氨蝶呤减少了大鼠在露天竞技场中央区域的停留时间,降低了高架加迷宫实验中张开双臂的停留时间,增加了悬尾实验中静止不动的时间。甲氨蝶呤引起海马CA3区神经元细胞数量减少,神经退行性和萎缩性改变。阿达木单抗改善了甲氨蝶呤相关的焦虑和抑郁样行为,并改善了组织病理学改变。本研究表明,阿达木单抗治疗可以预防甲氨蝶呤相关的焦虑和抑郁样行为障碍,但建议进一步研究阿达木单抗治疗效果的机制。
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Effect of tnf-alpha inhibitor on anxiety- and depression-like behaviors in a mouse chemobrain model
Although chemotherapy increases the survival rate of cancer patients, it causes significant side effects such as deterioration in cognitive functions that generate a decline in their living standards. In our study, the effect of adalimumab on anxiety- and depression-like behaviors in mice with cognitive impairment with methotrexate was investigated. In our study, methotrexate (40 mg kg-1) was administered intraperitoneally as a single dose to create a chemobrain model in mice. Adalimumab (10 mg kg-1), a TNF-alpha inhibitor, was administered twice, 1 hour and 5 days before methotrexate administration. Anxiety-like behaviors were measured with elevated plus maze test and open field test, depression-like behaviors were measured with tail suspension test, and hippocampal tissue was examined histopathologically. Methotrexate decreased the time spent in the central zone in the open-field arena, the time spent in the open arms in the elevated plus maze test, and increased the duration of immobility in the tail suspension test in rats. Methotrexate caused a decrease in the number of neuronal cells in the CA3 region of the hippocampus, as well as neurodegenerative and atrophic changes. Adalimumab ameliorated methotrexate-related anxiety- and depression-like behaviors, and caused improvement in histopathological changes. In this study, it was shown that methotrexate-related anxiety and depression-like behavioral disorders were prevented by adalimumab treatment, but further studies are recommended to investigate the mechanisms mediating the therapeutic effect of adalimumab.
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