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Article

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

1
Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia
2
Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technology, 394036 Voronezh, Russia
*
Author to whom correspondence should be addressed.
Academic Editors: Lusine Danielyan and Huu Phuc Nguyen
Pharmaceuticals 2021, 14(7), 607; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070607
Received: 27 May 2021 / Revised: 17 June 2021 / Accepted: 21 June 2021 / Published: 23 June 2021
(This article belongs to the Special Issue New Drugs and Biologics For Treatment of Central Nervous Dysfunction)
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 Roseburia, Oscillibacter, ChristensenellaceaeR-7, Negativibacillus, and Faecalibaculum 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. View Full-Text
Keywords: aging; cognitive dysfunction; Nrf2/ARE pathway; mitochondrial biogenesis; mitophagy; antioxidants; resveratrol; dimethyl fumarate; methylene blue; memory; gut–brain axis; gut microbiome aging; cognitive dysfunction; Nrf2/ARE pathway; mitochondrial biogenesis; mitophagy; antioxidants; resveratrol; dimethyl fumarate; methylene blue; memory; gut–brain axis; gut microbiome
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MDPI and ACS Style

Sadovnikova, I.S.; Gureev, A.P.; Ignatyeva, D.A.; Gryaznova, M.V.; Chernyshova, E.V.; Krutskikh, E.P.; Novikova, A.G.; Popov, V.N. Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome. Pharmaceuticals 2021, 14, 607. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070607

AMA Style

Sadovnikova IS, Gureev AP, Ignatyeva DA, Gryaznova MV, Chernyshova EV, Krutskikh EP, Novikova AG, Popov VN. Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome. Pharmaceuticals. 2021; 14(7):607. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070607

Chicago/Turabian Style

Sadovnikova, Irina S., Artem P. Gureev, Daria A. Ignatyeva, Maria V. Gryaznova, Ekaterina V. Chernyshova, Ekaterina P. Krutskikh, Anastasia G. Novikova, and Vasily N. Popov 2021. "Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome" Pharmaceuticals 14, no. 7: 607. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070607

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