title: Methylene blue improves sensorimotor phenotype and decreases anxiety in parallel with activating brain mitochondria biogenesis in mid-age mice.
abstract: 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.
authors: Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia.
authors: Artem P
authors: AP
authors: Gureev
authors: Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia.
authors: Mikhail Yu
authors: MY
authors: Syromyatnikov
authors: Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia.
authors: Tatyana M
authors: TM
authors: Gorbacheva
authors: Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY, USA. Electronic address: ans2024@med.cornell.edu.
authors: Anatoly A
authors: AA
authors: Starkov
authors: Department of Genetics, Cytology and Bioengineering, Voronezh State University, Voronezh, Russia. Electronic address: pvn@bio.vsu.ru.
authors: Vasily N
authors: VN
authors: Popov
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D001678:Organelle Biogenesis; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D008751:Methylene Blue
keywords: Aging; Behavior; Hydrogen peroxide; Methylene blue; Mitochondria