Methylene blue improves sensorimotor phenotype and decreases anxiety in parallel with activating brain mitochondria biogenesis in mid-age mice

• Published in: Neuroscience research Vol. 113; pp. 19 - 27
• Main Authors: Gureev, Artem P., Syromyatnikov, Mikhail Yu, Gorbacheva, Tatyana M., Starkov, Anatoly A., Popov, Vasily N.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2016
• Subjects: Aging; Animals; Antioxidant Response Elements; Anxiety - drug therapy; Anxiety - physiopathology; Anxiety - psychology; Behavior; Brain - drug effects; Brain - metabolism; Energy Metabolism; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Male; Maze Learning - drug effects; Methylene blue; Methylene Blue - pharmacology; Methylene Blue - therapeutic use; Mice, Inbred C57BL; Mitochondria; Motor Activity - drug effects; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Organelle Biogenesis; Reactive Oxygen Species - metabolism; Hydrogen peroxide; PTEN; CNS; Methylene blue; Nrf2/ARE; Mitochondria; PI3K; MB; ETC; ND; ROS; NRF-1; SOD1/2; Aging; TFAM; COX1; Behavior
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2016.07.006

•Methylene blue improves behavioral phenotype and physical strength in aging mice.•Methylene blue enhances the H2O2 formation rate in mouse brain mitochondria.•Methylene blue activates mitochondrial biogenesis via Nrf2/ARE signaling. Age-related brain dysfunctions are associated with mitochondria malfunctions and increased risk of developing neurodegenerative diseases (ND). Recently, a mitochondria-targeting drug methylene blue has been drawing considerable interest as a potential treatment for ND. We found that aged mice manifested a decrease in physical endurance, spontaneous locomotor activity, and exploration concomitant with an increase in anxiety-related behavior, as compared to adult mice. Treating mice for 60 days with MB slowed down these changes. There were no significant changes in the animals’ body weight, oxygen consumption rates, or respiratory quotient index, in adult or aged MB-treated mice. However, MB treatment significantly increased the generation of reactive oxygen species in brain mitochondria. The expression of several genes relevant to mitochondria biogenesis, bioenergetics, and antioxidant defense (NRF1, MTCOX1, TFAM, and SOD2) was greatly suppressed in aged mice; it was restored by MB treatment. It seems plausible that the effects of MB could be mediated by its ability to increase H2O2 production in brain mitochondria, thereby activating Nrf2/ARE signaling pathway and mitochondria biogenesis. Our data and earlier findings support the idea that MB can be an attractive prototype drug for developing safe and efficient gerontoprotective compounds.