Cyanidin Chloride 通过改善海马炎症和兴奋性毒性改善 LPS 诱导的小鼠抑郁样行为,ACS Chemical Neuroscience

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Cyanidin Chloride 通过改善海马炎症和兴奋性毒性改善 LPS 诱导的小鼠抑郁样行为
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2022-10-17 , DOI: 10.1021/acschemneuro.2c00087
Di Qu _{1,

2} , Zichen Ye ₃ , Wenli Zhang _{1,

2} , Bing Dai _{1,

2} , Guo Chen ₂ , Li Wang ₂ , Xiaolong Shao ₂ , An Xiang ₂ , Zifan Lu ₂ , Juan Shi ₄

Affiliation

抑郁症是一种全球性疾病，对人类健康造成重大负担。大脑区域（如海马）的神经炎症和谷氨酸代谢紊乱在抑郁症的发展中起着至关重要的作用。先前的研究表明，氰化物氯化物 (Cycl) 具有抗炎和抗氧化特性，对周围组织具有神经保护作用。然而，Cycl 对抑郁症的影响以及该化合物靶向大脑区域的可能机制仍未得到阐明。我们调查了 Cycl 在脂多糖 (LPS) 诱导的抑郁症中的作用，并检查了药物对中枢炎症和海马中兴奋性氨基酸转运蛋白表达的影响。我们发现预防性ip以 20 或 40 mg/kg 的剂量施用 Cycl 5 天，显着缩短了 LPS 攻击小鼠通过尾部悬吊试验 (TST) 和强迫游泳试验 (FST) 评估的不动时间，表明该药物具有有效的抗抑郁活性。海马体中的蛋白质印迹和免疫荧光染色显示，Cycl 抑制促炎细胞因子（包括 TNF-α 和 IL-6）的上调，并抑制 LPS 诱导的小胶质细胞过度活跃，表明在海马体中具有抗炎作用。此外，Cycl 治疗还恢复了胶质纤维酸性蛋白 (GFAP)、脑源性神经营养因子 (BDNF) 和谷氨酸-天冬氨酸转运蛋白 (GLAST) 和兴奋性氨基酸转运蛋白 2 (EAAT2) 的下调表达，这两个兴奋性氨基酸转运蛋白家族。Cycl 的作用也在培养的 BV2 和 U251 细胞中得到验证。总之，现体内和体外研究表明，Cycl 在 LPS 诱导的抑郁模型中发挥有效的抗抑郁作用，其潜在机制与海马炎症减少、神经营养功能改善和谷氨酸诱导的兴奋性毒性减弱有关。

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Cyanidin Chloride Improves LPS-Induced Depression-Like Behavior in Mice by Ameliorating Hippocampal Inflammation and Excitotoxicity

Depression is a global disease that places a significant burden on human health. Neuroinflammation and disturbance of glutamate metabolism in brain regions, such as the hippocampus, play vital roles in the development of depression. Previous studies have shown that cyanidin chloride (Cycl) has anti-inflammatory and antioxidant properties with neuroprotective effects in peripheral tissues. However, the effects of Cycl on depression and the possible mechanism by which this compound targets brain regions remain less elucidated. We investigated the role of Cycl in lipopolysaccharide (LPS)-induced depression and examined the influence of the drug on central inflammation and the expression of excitatory amino acid transporters in the hippocampus. We found that prophylactic i.p. application of Cycl at 20 or 40 mg/kg for 5 days significantly reduced the immobility time assessed by the tail suspension test (TST) and forced swim test (FST) in LPS-challenged mice, suggesting an effective antidepressant activity of the drug. Western blotting and immunofluorescence staining in the hippocampus revealed that Cycl inhibited the upregulation of proinflammatory cytokines, including TNF-α and IL-6, and suppressed the hyperactivity of microglia induced by LPS, indicating an anti-inflammatory role in the hippocampus. Moreover, treatment with Cycl also recovered the downregulated expression of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glutamate–aspartate transporter (GLAST) and excitatory amino acid transporter 2 (EAAT2), two members in the excitatory amino acid transporter family. The role of Cycl was also verified in cultured BV2 and U251 cells. In conclusion, the present in vivo and in vitro studies demonstrate that Cycl exerts potent antidepressant action in an LPS-induced depression model and the underlying mechanism is associated with reduced hippocampal inflammation, improved neurotrophic function, and attenuated excitotoxicity induced by glutamate.

更新日期：2022-10-17

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