Methylene blue improves brain oxidative metabolism and memory retention in rats

Abstract

Methylene blue (MB) increases mitochondrial oxygen consumption and restores memory retention in rats metabolically impaired by inhibition of cytochrome c oxidase. This study tested two related hypotheses using biochemical and behavioral techniques: (1) that low-level MB would enhance brain cytochrome c oxidation, as tested in vitro in brain homogenates and after in vivo administration to rats and (2) that corresponding low-dose MB would enhance spatial memory retention in normal rats, as tested 24 h after rats were trained in a baited holeboard maze for 5 days with daily MB posttraining injections. The biochemical in vitro studies showed an increased rate of brain cytochrome c oxidation with the low but not the high MB concentrations tested. The in vivo administration studies showed that the corresponding MB low dose (1 mg/kg) increased brain cytochrome c oxidation 24 h after intraperitoneal injection, but not after 1 or 2 h postinjection. In the behavioral studies, spatial memory retention in probe trials (percentage of visits to training-baited holes compared to total visits) was significantly better for MB-treated than saline control groups (66% vs. 31%). Together the findings suggest that low-dose MB enhances spatial memory retention in normal rats by increasing brain cytochrome c oxidase activity.