非那雄胺长期和短期治疗对早衰雄性大鼠焦虑样和抑郁样行为的比较效应

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Hiranya Pintana, Nattayaporn Apaijai, Titikorn Chunchai, Chanisa Thonusin, Thiraphat Saengmearnuparp, Aphisek Kongkaew, Nipon Chattipakorn, Siriporn C. Chattipakorn
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引用次数: 0

摘要

本研究旨在比较5-α-还原酶抑制剂(5ARIs)对d-半乳糖(Dgal)诱导的衰老雄性大鼠长期治疗和短期治疗后停药对焦虑和抑郁的疗效。32 只 8 周大的雄性 Wistar 大鼠被分为两组:对照组和 Dgal 治疗组(150 毫克/千克/天;皮下注射),为期 18 周。第 13 周时,Dgal 治疗大鼠被分为三个亚组:(1) 对照组(DgV);(2) 5ARIs 长期治疗组(DgF);(3) 5ARIs 短期治疗组(DgW);(4) 非那雄胺 5 mg/kg/day 口服治疗组(DgW)。焦虑和抑郁通过高架迷宫(EPM)和泼溅试验(ST)进行评估。采集血液进行生化分析。安乐死后,取出大鼠大脑,检查脑部炎症、氧化应激、神经活性类固醇、脑代谢物和脑衰老标志物。我们发现,DgV大鼠表现出代谢紊乱,EPM的偏好指数和ST的梳理持续时间降低。我们观察到,DgV大鼠脑部神经毒性代谢物增加,脑部炎症/氧化应激增加,小胶质细胞复杂性降低。两种治疗方法都能改善 Dgal 治疗大鼠 EPM 开放臂的代谢参数和偏好指数,而只有 DgF 治疗大鼠的梳理持续时间和小胶质细胞复杂性有所增加。我们的研究结果表明,芬通过减少脑部炎症、氧化应激和脑衰老来减少抑郁样和焦虑样行为。总之,在Dgal诱导的早衰雄性大鼠中,5ARIs的长期治疗比短期治疗后停药更能有效缓解抑郁。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Comparative Effects Between Long-Term and Short-Term Treatment of Finasteride on Anxiety-Like and Depression-Like Behaviors in Early Senescent Male Rats

This study aims to compare the efficacy of 5-alpha-reductase inhibitors (5ARIs) on anxiety and depression between long-term and short-term treatment followed by withdrawal in d-galactose (Dgal)–induced senescent male rats. Thirty-two, 8-week-old, male Wistar rats were divided into two groups: control rats and Dgal-treated rats (150 mg/kg/day; subcutaneously) for 18 weeks. At week 13, Dgal-treated rats were subdivided into three subgroups: (1) vehicle (DgV), (2) long-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 6 weeks (DgF), (3) short-term treatment with 5ARIs, Finasteride 5 mg/kg/day, per oral for 2 weeks followed by a 4-week withdrawal period (DgW). Anxiety and depression were assessed using the elevated-plus maze (EPM) and splash test (ST). Blood was collected for biochemical analysis. After euthanasia, the brains were removed to examine brain inflammation, oxidative stress, neuroactive steroids, brain metabolites, and brain senescent markers. We found that DgV rats exhibited metabolic disturbance with a reduced preference index of the EPM, and grooming duration in ST. Increased brain neurotoxic metabolites, along with increased brain inflammation/oxidative stress, and reduced microglia complexity were observed in the DgV rats. Both therapeutic approaches improved metabolic parameters and preference index in the open arm of EPM in Dgal-treated rats, while grooming duration and microglia complexity were increased only in DgF rats. Our results indicate that Fin reduces depression-like and anxiety-like behaviors by reducing brain inflammation, oxidative stress, and brain senescent. In conclusion, long-term treatment with 5ARIs is more effective in alleviating depression than short-term treatment followed by withdrawal in Dgal-induced early senescent male rats.

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来源期刊
Journal of Neuroscience Research
Journal of Neuroscience Research 医学-神经科学
CiteScore
9.50
自引率
2.40%
发文量
145
审稿时长
1 months
期刊介绍: The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.
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