Abstract Context: Experiencing early-life adversity plays a key role in the development of mood disorders in adulthood. Experiencing adversities during early life period negatively affects brain development. Sex steroids such as progesterone affect the brain structure and functions and subsequently affects behaviour. Objective: We assess the antidepressant-like effect of progesterone in a mouse model of maternal separation (MS) stress, focussing on its anti-neuroinflammatory and antioxidative effects. Materials and methods: NMRI mice were treated with progesterone (10, 50, and 100 mg/kg, i.p., respectively) for 14 days. Valid behavioural tests including forced swimming test (FST), splash test and open field test (OFT) were used. Quantitative reverse transcription-PCR (qRT-PCR) was used for evaluation of genetic expression in the hippocampus. Antioxidant capacity was assessed by the FRAP method and the level of malondialdehide by TBA. Results: MS provoked depressive-like behaviour in mice. Treatment of MS mice with progesterone increased the grooming activity time in the splash test and decreased the immobility time in the FST. In addition, progesterone decreased the expression of inflammatory genes related to neuroinflammation (IL-1β, TNF-α, TLR4 and NLRP3) as well as increased the antioxidant capacity and decreased the lipid peroxidation (MDA) in the hippocampus. Discussion and Conclusion: Administration of progesterone significantly mitigated the negative effects of MS on behaviours relevant to depressive-like behaviour as well as attenuated neuro-immune response and oxidative stress in the hippocampus of MS mice. In this context, we conclude that progesterone, at least partially, via attenuation of oxidative stress and neuroinflammation, exerts antidepressant-like effects.

中文翻译：

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孕酮通过减轻神经炎症反应和氧化应激在母体分离应激小鼠模型中发挥抗抑郁样作用

摘要背景：经历早期生活的逆境在成年期情绪障碍的发展中起着关键作用。在生命早期经历逆境会对大脑发育产生负面影响。黄体酮等性类固醇会影响大脑结构和功能，进而影响行为。目的：我们评估孕酮在母体分离 (MS) 应激小鼠模型中的抗抑郁样作用，重点是其抗神经炎症和抗氧化作用。材料和方法：NMRI 小鼠用孕酮（分别为 10、50 和 100 mg/kg，ip）治疗 14 天。使用了有效的行为测试，包括强迫游泳测试（FST）、飞溅测试和露天测试（OFT）。定量逆转录 PCR (qRT-PCR) 用于评估海马中的基因表达。抗氧化能力通过 FRAP 方法评估，丙二醛水平通过 TBA 评估。结果：MS 在小鼠中引起抑郁样行为。用孕酮治疗 MS 小鼠增加了飞溅测试中的梳理活动时间并减少了 FST 中的不动时间。此外，黄体酮降低了与神经炎症相关的炎症基因（IL-1β、TNF-α、TLR4 和 NLRP3）的表达，并增加了抗氧化能力并降低了海马中的脂质过氧化（MDA）。讨论和结论：孕酮的给药显着减轻了 MS 对与抑郁样行为相关的行为的负面影响，以及减弱了 MS 小鼠海马中的神经免疫反应和氧化应激。在这种情况下，我们得出结论，孕酮，至少部分，