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Nrf2/ARE激活剂通过维持大脑线粒体质量控制和调节肠道微生物群来改善老年小鼠的记忆力。

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome.

作者信息

Sadovnikova Irina S, Gureev Artem P, Ignatyeva Daria A, Gryaznova Maria V, Chernyshova Ekaterina V, Krutskikh Ekaterina P, Novikova Anastasia G, Popov Vasily N

机构信息

Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia.

Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technology, 394036 Voronezh, Russia.

出版信息

Pharmaceuticals (Basel). 2021 Jun 23;14(7):607. doi: 10.3390/ph14070607.

DOI:10.3390/ph14070607
PMID:34201885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8308546/
Abstract

Aging is one of the most serious factors for central nervous dysfunctions, which lead to cognitive impairment. New highly effective drugs are required to slow the development of cognitive dysfunction. This research studied the effect of dimethyl fumarate (DMF), methylene blue (MB), and resveratrol (RSV) on the cognitive functions of 15-month-old mice and their relationship to the maintenance of mitochondrial quality control in the brain and the bacterial composition of the gut microbiome. We have shown that studied compounds enhance mitochondrial biogenesis, mitophagy, and antioxidant defense in the hippocampus of 15-month-old mice via Nrf2/ARE pathway activation, which reduces the degree of oxidative damage to mtDNA. It is manifested in the improvement of short-term and long-term memory. We have also shown that memory improvement correlates with levels of , and genera of bacteria. At the same time, long-term treatment by MB induced a decrease in gut microbiome diversity, but the other markers of dysbiosis were not observed. Thus, Nrf2/ARE activators have an impact on mitochondrial quality control and are associated with a positive change in the composition of the gut microbiome, which together lead to an improvement in memory in aged mice.

摘要

衰老中枢神经功能障碍的最严重因素之一，会导致认知障碍。需要新型高效药物来减缓认知功能障碍的发展。本研究探讨了富马酸二甲酯（DMF）、亚甲蓝（MB）和白藜芦醇（RSV）对15月龄小鼠认知功能的影响，以及它们与维持大脑线粒体质量控制和肠道微生物群细菌组成的关系。我们发现，所研究的化合物通过激活Nrf2/ARE通路，增强了15月龄小鼠海马体中的线粒体生物合成、线粒体自噬和抗氧化防御，减少了mtDNA的氧化损伤程度。这表现为短期和长期记忆的改善。我们还发现，记忆改善与某些细菌属的水平相关。同时，MB长期治疗导致肠道微生物群多样性降低，但未观察到其他生态失调标志物。因此，Nrf2/ARE激活剂对线粒体质量控制有影响，并与肠道微生物群组成的积极变化相关，二者共同导致老年小鼠记忆力的改善。

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