Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like behavior by reducing hippocampal neuroinflammation
Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like behavior by reducing hippocampal neuroinflammation
复制标题
辛伐他汀治疗青春期小鼠通过减少海马神经炎症来减轻 HFD 诱导的抑郁样行为
DOI：
10.1016/j.jad.2018.09.022
复制
发表时间：
2019-01-15
影响因子：
6.6
通讯作者：
Shang, Jing
中科院分区：
文献类型：
--
作者：
Wu, Huali;Lv, Wenting;Shang, Jing
背景资料：高脂饮食（HFD）诱导的肥胖/高脂血症伴随着激素和神经化学变化，可能与抑郁症有关。新的研究表明，辛伐他汀（SMV，降低胆固醇水平）通过代谢依赖性功能对神经和神经精神疾病具有治疗作用。然而，在青春期动物中暴露于HFD，研究SMV对海马形态学、5-HT系统和炎症的神经保护作用的研究有限。因此，本研究的目的是确定SMV是否减弱HFD诱导的抑郁症在青春期动物，更具体地说，作为一种抗神经炎症反应。方法：24只雄性C57 BL/6小鼠喂养对照组（n = 8），HFD（n = 8）和HFD + SMV（n = 8）为14周。HFD + SMV组从HFD喂养第10周开始给予SMV（10 mg/kg）。采用旷场试验和悬尾试验研究SMV对行为学的影响。HE染色和Nissl染色观察海马形态和神经元存活情况。定量聚合酶链反应（Q-PCR）检测炎症细胞因子基因的表达。结果：首先，SMV治疗后血脂指标的变化最小化。HFD诱导的抑郁样行为，这是证明了增加不动时间在TST沿着相当大的减少运动活动，SMV治疗4周显着减弱。此外，SMV可减轻HFD引起的海马结构异常、神经元损伤、神经元能系统紊乱和促炎细胞因子的过度表达。海马中央区的神经免疫学变化与外周脾区的变化相似（仅IL-1 β、IL-6、TNF-α），而与大脑皮质区的变化趋势相反。结论：SMV可能通过脑区特异性的神经炎症机制治疗HFD诱导的青春期抑郁样行为。
Background: A high-fat diet (HFD)-induced obesity/hyperlipidemia is accompanied by hormonal and neurochemical changes that can be associated with depression. Emerging studies indicate that simvastatin (SMV, decreasing cholesterol levels) has therapeutic effects on neurological and neuropsychiatric diseases through hippocampal-dependent function. However, the studies on the HFD exposure in adolescent animals, which investigate the neuroprotective effects of SMV on the hippocampal morphology, serotonin (5-HT) system and inflammation, are limited. Hence, the aim of this study was to determine whether SMV attenuates HFD-induced major depressive disorders in adolescent animals and, more specifically, acts as an anti-neuroinflammatory response.Methods: Twenty-four male C57BL/6 mice were fed a control (n = 8), HFD (n = 8) and HFD + SMV (n = 8) for 14 weeks. In HFD + SMV group, SMV (10 mg/kg) was administrated from the 10th week of HFD feeding. The open field test (OFT) and the tail suspension test (TST) were used to examine the effect of SMV on behavioral performance. HE and Nissl staining were conducted to detect hippocampal morphology and neural survival. Expression of the inflammatory cytokine genes was assayed by quantitative polymerase chain reaction (Q-PCR).Results: Firstly, alterations in lipid parameters were minimized after SMV treatment. HFD-induced depression-like behavior, which was evidenced by an increase in immobility time in TST along with considerable decrease in locomotion activity, was significantly attenuated by SMV therapy for 4 weeks. Additionally, SMV could reduce HFD-induced structural abnormality, neuronal injury, serotonergic system disturbance and pro-inflammatory cytokine over-expression in the hippocampus. Neuroimmunological changes in central hippocampus displayed a similar characteristic (only IL-1 beta, IL-6, TNF-alpha) with that in periphery spleen, whereas they appeared in an entirely opposite trend with that in cerebral cortex.Conclusion: Our results suggest that SMV may be a promising treatment for HFD-induced depression-like behavior during adolescent period through brain region-specific neuroninflammatory mechanisms.