Methylene blue improves brain oxidative metabolism and memory retention in rats

The brain metabolic enhancer methylene blue improves discrimination learning in rats

“…Methylene blue (MB) is a brain metabolic enhancer that has been demonstrated to improve memory retention when given post-training in low doses in a variety of simple appetitive and aversive learning tasks in rats (Callaway et al 2002(Callaway et al ,2004Gonzalez-Lima and Bruchey, 2004;Martinez Jr et al 1978;Riha et al 2005). The present results indicate that MB could also facilitate more complex learning such as in discrimination tasks that require repeated days of training.…”

“…These results suggested that MB could facilitate the memory consolidation occurring in the brain following a learning session. Independent studies in our laboratory have supported this interpretation by showing that post-training MB increases memory retention in appetitive, aversive and spatial learning tasks, such as in object recognition, between-days habituation to a familiar environment, and spatial memory retention and reversal learning in the baited holeboard maze (Callaway et al 2002(Callaway et al ,2004Riha et al 2005). also found that memory retention of extinction of Pavlovian fear conditioning was enhanced with post-extinction administration of MB, and that this effect was related to an increase in brain cytochrome oxidase activity.…”

“…The goal of the first experiment was to investigate the memory retention effects of daily 1 mg/kg MB on a discrimination learning task in the holeboard maze, using an appetitive spatial memory task that requires repeated days of training. Since previous studies demonstrated an improvement in spatial memory retention in the holeboard maze food search task following MB administration (Callaway et al 2002(Callaway et al ,2004, we were interested in further investigating its effects on the more demanding discrimination learning of rewarded versus non-rewarded trials in the maze.…”

“…The number of daily injections was chosen based on the behavioral data from the first experiment which revealed group differences three days after the beginning of MB treatment. It was hypothesized that brain cytochrome oxidase activity in the MB-treated group would be higher than in saline-treated rats, leading to increased brain metabolic energy capacity (Callaway et al 2004;Gonzalez-Lima and Bruchey, 2004).…”

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…In a randomized, double-blind, multicenter study with 450 participants with mild-to-moderate AD, Idebenone showed minimal cognitive benefit [69][70][71], but was not approved for treatment of AD based on results not reaching statistical significance in larger trials [70][71][72]. Methylene blue can enhance cytochrome c oxidase activity through direct electron donation [80,81]. In a preclinical AD mouse model, methylene blue treatment reduced Tau-neurofibrillary tangle burden [82].…”