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首页> 外文期刊>Frontiers in Neuropharmacology >Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats
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Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats

机译：Harmine通过抑制NLRP3炎症组激活并增强STZ诱导的糖尿病大鼠中的BDNF / TRKB信号通路来改善认知障碍

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Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction.
机译：糖尿病（DM）被认为是认知功能障碍的危险因素。 Harnine不仅有效改善DM的症状，还可以在中枢神经系统疾病中提供神经保护作用。然而，伤害是否对糖尿病诱导的认知功能障碍的影响，并且潜在的机制仍然未知。在这项研究中，通过Morris水迷宫测试评估了大鼠的学习和记忆能力。在链脲佐佐菌素（STZ）中，确定含核苷酸结合吲哚胺蛋白（NOD）的含有3（NLRP3）炎症组和脑衍生的神经营养因子（BDNF）/ TRKB信号传导途径的吡隆结构域的变化糖尿病大鼠和高葡萄糖（Hg）-Treated SH-SY5Y细胞通过蛋白质印迹和组织化学。在此，我们发现糖尿病大鼠中的肿瘤给药显着改善了学习和记忆障碍。进一步的研究表明，大问题抑制了NLRP3炎症体活化，如通过降低的NLRP3，ASC，切割的Caspase-1，IL-1β和IL-18水平，在用DM的调谐后的大鼠皮层中证明。观察到HAG治疗的神经元细胞中具有类似的有益效果。此外，我们发现，HARINE治疗增强了STZ诱导的糖尿病大鼠和HG处理细胞的皮质中的BDNF和磷酸化TRKB水平。这些数据表明，通过抑制NLRP3炎症组激活并增强BDNF / TRKB信号通路来减轻认知障碍。因此，我们的研究结果表明，Harmine是糖尿病诱导的认知功能障碍的潜在治疗药物。

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