Methylene Blue Attenuates Impaired Cognitive Functions and Reduces Hippocampal Aβ Levels and Oxidative Stress in D-Galactose-Induced Alzheimer’s Disease Mouse Model

Abstract

Methylene blue (MB) has a long story of use and has been employed for various diseases, however, most of its current rekindled research is related to its function in the mitochondria. MB is gaining interest as a possible treatment because mitochondrial dysfunction is an apparent unifying pathogenic characteristic of a variety of neurodegenerative conditions. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairment of cognitive functions. This study aims to investigate whether MB treatment improves impaired cognitive functions and reduces hippocampal amyloid-β levels and oxidative stress in a D-galactose-induced AD mouse model. Twenty-four wild-type Balb/c mice were randomly divided into four groups (control, D-galactose-induced AD, MB-treated AD, and only MB-treated mice). Mice in the corresponding groups were injected with D-galactose (50 mg/kg, s.c.) for 60 days. In the MB treatment groups, the mice were treated with MB (2 mg/kg, orally) for the last 14 days of treatments. The Morris water maze test was used to assess spatial learning and memory functions. Amyloid β-42, malondialdehyde, superoxide dismutase, and nitric oxide levels in the hippocampi of mice were measured using ELISA and spectrophotometry. MB treatment improved impaired learning and memory functions induced by D-galactose administration and decreased amyloid β-42 concentration in the hippocampi of mice. Malondialdehyde level was found to decrease in MB-treated mice compared to D-galactose-induced AD mice in the hippocampus and plasma. The hippocampus of MB-treated mice displayed increased superoxide dismutase activity while decreased nitric oxide concentration compared to the ones of D-galactose-induced AD mice. MB has been shown to improve learning and memory impairments, as well as reduce Aβ-42 concentration and oxidative stress in the hippocampus of D-galactose-induced AD mice. The findings of this study demonstrate that MB may offer potential benefits as a repurposed agent for AD.