PDF(Pubmed)
Abstract：
The pathological consequences of type 2 diabetes mellitus (T2DM) also involve the central nervous system; indeed, T2DM patients suffer from learning and memory disabilities with a higher risk of developing dementia. Although several factors have been proposed as possible contributors, how neuroactive steroids and the gut microbiome impact brain pathophysiology in T2DM remain unexplored. On this basis, in male Zucker diabetic fatty (ZDF) rats, we studied whether T2DM alters memory abilities using the novel object recognition test, neuroactive steroid levels by liquid chromatography-tandem mass spectrometry, hippocampal parameters using molecular assessments, and gut microbiome composition using 16S next-generation sequencing. Results obtained reveal that T2DM worsens memory abilities and that these are correlated with increased levels of corticosterone in plasma and with a decrease in allopregnanolone in the hippocampus, where neuroinflammation, oxidative stress, and mitochondrial dysfunction were reported. Interestingly, our analysis highlighted a small group of taxa strictly related to both memory impairment and neuroactive steroid levels. Overall, the data underline an interesting role for allopregnanolone and microbiota that may represent candidates for the development of therapeutic strategies.
摘要：
2型糖尿病（T2DM）的病理后果也涉及中枢神经系统;事实上，T2DM患者患有学习和记忆障碍，患痴呆症的风险更高。尽管已经提出了几个因素作为可能的贡献者，神经活性类固醇和肠道微生物组如何影响T2DM的脑部病理生理学仍未被研究.在此基础上,在雄性Zucker糖尿病脂肪（ZDF）大鼠中，我们使用新颖的对象识别测试研究了T2DM是否会改变记忆能力，通过液相色谱-串联质谱法测定神经活性类固醇水平，使用分子评估的海马参数，和使用16S下一代测序的肠道微生物组组成。获得的结果表明，T2DM使记忆能力恶化，这些与血浆中皮质酮水平升高和海马中别孕烯醇酮的减少有关。神经炎症，氧化应激，和线粒体功能障碍的报道。有趣的是,我们的分析强调了一小组与记忆障碍和神经活性类固醇水平严格相关的分类群.总的来说,数据强调了别孕烯醇酮和微生物群的有趣作用,它们可能代表了治疗策略开发的候选者.
