Department of Pharmacy, Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, the First Affiliated Hospital of Wenzhou Medical University, 325000, China.
Department of Pharmacy, Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, the First Affiliated Hospital of Wenzhou Medical University, 325000, China; Department of Pharmacy, University of Pittsburgh, PA 15260, United States.
J Affect Disord. 2019 Feb 15;245:939-949. doi: 10.1016/j.jad.2018.11.086. Epub 2018 Nov 13.
Statins play a beneficial role in the treatment of coronary artery disease and are widely prescribed to prevent hypercholesterolemia. Previous studies have demonstrated that statins also have anti-inflammatory and immunomodulatory properties, and these are being explored for potential benefits in depression. However, the role of statins in the treatment of depression has not been well examined.
We investigated the effects of simvastatin on depressive behaviors and neuroinflammation in lipopolysaccharide (LPS) and chronic mild stress (CMS) induced depression model in mice. Sucrose preference test (SPT), forced swimming test (FST), novelty-suppressed feeding test (NSFT) were used to detect the depressive behaviors. The microglial activation was detected by immunohistochemistry analysis and the pro-inflammatory cytokines expressions including IL-1β, TNF-α and IL-6 were examined by Western blot analysis.
Our data indicated that oral administration of simvastatin at 20 mg/kg significantly prevented and ameliorated depressive behaviors reflected by better performance in the SPT, FST and NSFT. Moreover, simvastatin markedly prevented and ameliorated LPS and CMS-induced neuroinflammation, as shown by the suppressed activation of microglia in hippocampus and decreased hippocampal pro-inflammatory cytokines expressions including IL-1β, TNF-α, IL-6, which might be mediated via the inhibition of NF-κB pathway, as shown by the decreased nuclear NF-κB p65 expression.
The interpretation of the evidence of a positive treatment effect of simvastatin on the depressive manifestations, multifaceted etiology of depression, and confirmation of this finding from animal models to humans is needed.
These results suggest that simvastatin has the potential to be employed as a therapy for depression associated with neuroinflammation.
他汀类药物在治疗冠状动脉疾病方面发挥着有益的作用，被广泛用于预防高胆固醇血症。先前的研究表明，他汀类药物还具有抗炎和免疫调节特性，这些特性正在被探索用于抑郁症的潜在益处。然而，他汀类药物在治疗抑郁症中的作用尚未得到充分研究。
我们研究了辛伐他汀对脂多糖（LPS）和慢性轻度应激（CMS）诱导的抑郁模型中小鼠抑郁行为和神经炎症的影响。采用蔗糖偏好试验（SPT）、强迫游泳试验（FST）、新异环境抑制摄食试验（NSFT）检测抑郁行为。免疫组织化学分析检测小胶质细胞激活，Western blot 分析检测促炎细胞因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达。
我们的数据表明，辛伐他汀 20mg/kg 口服给药可显著预防和改善 LPS 和 CMS 诱导的抑郁行为，表现在 SPT、FST 和 NSFT 中的表现更好。此外，辛伐他汀可显著预防和改善 LPS 和 CMS 诱导的神经炎症，表现为海马小胶质细胞激活受到抑制，海马促炎细胞因子表达包括 IL-1β、TNF-α、IL-6 降低，这可能是通过抑制 NF-κB 通路介导的，表现为核 NF-κB p65 表达减少。
需要解释辛伐他汀对抑郁表现的积极治疗效果的证据，考虑到抑郁症的多因素病因，并从动物模型到人类确认这一发现。
这些结果表明，辛伐他汀有可能被用作治疗与神经炎症相关的抑郁症的药物。
