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Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome
- Source :
- Pharmaceuticals, Vol 14, Iss 607, p 607 (2021), Pharmaceuticals, Volume 14, Issue 7
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
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 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.
- Subjects :
- mitochondrial biogenesis
Gut–brain axis
gut microbiome
Pharmaceutical Science
Hippocampus
resveratrol
Resveratrol
Biology
Article
memory
chemistry.chemical_compound
Pharmacy and materia medica
cognitive dysfunction
Memory improvement
Drug Discovery
Mitophagy
medicine
gut–brain axis
dimethyl fumarate
aging
medicine.disease
biology.organism_classification
Cell biology
RS1-441
mitophagy
antioxidants
chemistry
Mitochondrial biogenesis
methylene blue
Medicine
Molecular Medicine
Nrf2/ARE pathway
Roseburia
Dysbiosis
Subjects
Details
- ISSN :
- 14248247
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Pharmaceuticals
- Accession number :
- edsair.doi.dedup.....c57c7fc7f227eba5436040d4af0e60a7
- Full Text :
- https://doi.org/10.3390/ph14070607