Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model
Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model
复制标题
二甲双胍通过调节肥胖小鼠模型的肠道微生物群恢复海马神经发生以及学习和记忆
DOI：
10.1016/j.bbi.2021.02.011
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发表时间：
2021-06-04
影响因子：
15.1
通讯作者：
Yan, Huanhuan
中科院分区：
文献类型：
--
作者：
Ma, Xiaoyi;Xiao, Wenchang;Yan, Huanhuan
大量研究表明，过度营养性肥胖可能导致糖尿病前期、2型糖尿病和认知能力下降。随着代谢紊乱程度的加重，认知能力的下降也越来越严重。然而，导致这种认知功能障碍的细胞事件尚未澄清。我们使用高脂饮食（HFD）消耗诱导的肥胖小鼠模型来测试二甲双胍对肥胖小鼠海马神经发生和学习记忆能力的影响。5-溴脱氧尿苷（BrdU）标记和逆转录病毒标记法检测海马新生神经元。行为学实验检测小鼠学习记忆能力。进行16 S rRNA基因测序以检测肠道菌群的组成。采用正电子发射断层扫描（PET）技术检测小鼠不同脑区的能量代谢活动。我们的研究结果表明，二甲双胍恢复齿状回神经发生的损伤，并最终防止肥胖小鼠的认知能力下降。此外，二甲双胍的治疗作用是通过调节小鼠肠道微生物群的组成来实现的，这可能会抑制肥胖小鼠大脑中的小胶质细胞活化和神经炎症。这项研究表明，二甲双胍可能是一个有希望的候选干预与肥胖引起的肠道微生物群失衡相关的认知下降。
Numerous studies have shown that over-nutritional obesity may lead to pre-diabetes, type 2 diabetes and cognitive decline. As the degree of metabolic disorders increases, the cognitive decline is getting worse. However, the cellular events that cause this cognitive dysfunction is yet to be clarified. We used a high-fat diet (HFD) consumption-induced obesity mouse model to test the effects of metformin on the hippocampal neurogenesis and learning and memory abilities of obese mice. 5-Bromo-2 '-deoxyuridine (BrdU) labelling and retrovirus labeling were applied to detect hippocampal newborn neurons. Behavioral experiments were used to detect learning and memory abilities of mice. 16S rRNA gene sequencing was performed to detect the composition of gut microbiota. The positron emission tomography (PET) was conducted to detect the energy metabolism activity of different mouse brain regions. Our results reveal that metformin restores the impairment of neurogenesis in the dentate gyrus and finally prevents the cognitive decline of the obese mice. Moreover, the therapeutic effects of metformin are achieved by regulating the composition of gut microbiota of mice, which may inhibit microglia activation and neuroinflammation in the brain of obese mice. This study suggests that metformin may be taken as a promising candidate for the intervention of cognitive decline related to imbalance of gut microbiota caused by obesity.