Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Biochemistry, Faculty of Pharmacy, October 6 University, Cairo, Egypt.
Brain Res. 2018 Dec 15;1701:227-236. doi: 10.1016/j.brainres.2018.09.027. Epub 2018 Sep 20.
Chronic stress occurs in everyday life and induces depression. Emerging evidence shows that oxidative stress, inflammation and apoptosis are main contributing pathophysiologic mechanisms of depression. Resveratrol and dimethyl fumarate (DMF) are natural antioxidants that have diverse biological activities. Our study aimed to determine whether resveratrol and DMF affected these systems in rats exposed to chronic unpredictable mild stress (CUMS)-induced depression-like behaviours. Rats were submitted to 8 weeks of CUMS to induce depressive-like behaviour. The depressive-like behaviour of rats induced by CUMS was revealed by an elevated serum corticosterone level and decreased serum and hippocampal serotonin levels. Our results showed that CUMS significantly-induced behavioural abnormalities (reduced sucrose preference and increased immobility time) in stressed rats. CUMS exposure significantly decreased BDNF and β-catenin expression levels as well as increased GSK-3β expression level in hippocampus. Furthermore, CUMS exposure resulted in a significant increase in expression levels of NF-κB, TNF-α and IL-Iβ accompanied by decreased Bcl-2 expression level. CUMS increased hippocampal MDA level and significantly decreased hippocampal GSH and serum total antioxidant capacity levels compared to the control group. Histopathological examinations provided evidence for the biochemical and molecular analysis. All of these effects were significantly ameliorated by administration of resveratrol and DMF. In conclusion, our study revealed that resveratrol and DMF exerted promising antidepressant-like effects in CUMS rats that are mediated in part by suppressing the neuroinflammation, oxidative stress, apoptosis and up-regulating hippocampal BDNF and β-catenin levels. Serum serotonin analysis may be a reliable indicator for monitoring depression.
慢性应激存在于日常生活中，并会引发抑郁。新出现的证据表明，氧化应激、炎症和细胞凋亡是抑郁的主要病理生理机制。白藜芦醇和富马酸二甲酯（DMF）是具有多种生物活性的天然抗氧化剂。我们的研究旨在确定白藜芦醇和 DMF 是否会影响慢性不可预测轻度应激（CUMS）诱导的抑郁样行为大鼠的这些系统。大鼠接受 8 周 CUMS 以诱导抑郁样行为。CUMS 诱导的大鼠抑郁样行为表现为血清皮质酮水平升高，血清和海马体 5-羟色胺水平降低。我们的结果表明，CUMS 显著诱导应激大鼠出现行为异常（减少蔗糖偏好和增加不动时间）。CUMS 暴露显著降低了海马体中的 BDNF 和 β-连环蛋白表达水平，同时增加了 GSK-3β 的表达水平。此外，CUMS 暴露导致 NF-κB、TNF-α 和 IL-Iβ 的表达水平显著增加，同时 Bcl-2 的表达水平降低。与对照组相比，CUMS 增加了海马体 MDA 水平，显著降低了海马体 GSH 和血清总抗氧化能力水平。组织病理学检查为生化和分子分析提供了证据。白藜芦醇和 DMF 的给药显著改善了所有这些影响。总之，我们的研究表明，白藜芦醇和 DMF 在 CUMS 大鼠中表现出有希望的抗抑郁样作用，部分通过抑制神经炎症、氧化应激、细胞凋亡以及上调海马体 BDNF 和 β-连环蛋白水平来发挥作用。血清 5-羟色胺分析可能是监测抑郁的可靠指标。
