Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences
Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences
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DOI：
10.1007/s00213-010-2094-2
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发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Chopra, Kanwaljit
中科院分区：
文献类型：
--
作者：
Kumar, Baldeep;Kuhad, Anurag;Chopra, Kanwaljit
压力情况、身体对压力的反应和临床抑郁症的发作之间存在着复杂的关系。慢性不可预测的应激源会产生类似于临床抑郁症的情况，此类动物模型可用于抗抑郁药的临床前评价。许多研究结果表明，抑郁症患者的促炎细胞因子（例如 TNF-α）和氧化应激（脂质过氧化增加、谷胱甘肽水平降低和内源性抗氧化酶活性）水平升高。芝麻酚是一种带有亚甲二氧基的酚类衍生物，是细胞因子产生的有效抑制剂，同时也是一种抗氧化剂。本研究旨在研究芝麻酚对小鼠不可预测的慢性应激诱导的行为和生化改变的影响。动物每天接受不同的应激模式，持续 21 天，以诱导抑郁样行为。评估了蔗糖偏好、不动时间、运动活性、记忆获取和保留。芝麻酚的长期治疗显着逆转了不可预测的慢性应激诱发的行为（不动时间增加、蔗糖偏好减少）、生化（脂质过氧化和亚硝酸盐水平增加；谷胱甘肽水平、超氧化物歧化酶和过氧化氢酶活性降低）和 应激小鼠的炎症激增（血清 TNF-α）。该研究表明，芝麻酚在长期应激小鼠的行为绝望范式中发挥抗抑郁样作用，特别是通过调节中枢氧化亚硝化应激和炎症。
A complex relationship exists among stressful situations, body's reaction to stress, and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-alpha) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Sesamol, a phenolic derivative with a methylenedioxy group, is a potent inhibitor of cytokine production as well as an antioxidant.The present study was designed to investigate the effect of sesamol on unpredictable chronic stress-induced behavioral and biochemical alterations in mice.Animals were subjected to different stress paradigms daily for a period of 21 days to induce depressive-like behavior. The sucrose preference, immobility period, locomotor activity, memory acquisition, and retention were evaluated.Chronic treatment with sesamol significantly reversed the unpredictable chronic stress-induced behavioral (increased immobility period, reduced sucrose preference), biochemical (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities), and inflammation surge (serum TNF-alpha) in stressed mice.The study revealed that sesamol exerted antidepressant-like effects in behavioral despair paradigm in chronically stressed mice, specifically by modulating central oxidative-nitrosative stress and inflammation.