Improvement of Spontaneous Locomotor Activity in a Murine Model of Duchenne Muscular Dystrophy by N-Acetylglucosamine Alone and in Combination With Prednisolone

Abstract

N-acetylglucosamine (GlcNAc) is an endogenous compound with intracellular concentration closely linked to the biosynthesis of acetyllactosamine-rich N-linked oligosaccharides. These oligosaccharides interact with mammalian lectin galectin-3, mediating cell surface receptor dynamics as well as cell–cell and cell-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, enhances muscle regeneration in vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in mdx mice, a murine model of Duchenne muscular dystrophy (DMD). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Daily treatment with United States Pharmacopeia-grade GlcNAc at doses of 0.6, 1.2, 1.8, and 2.4 g/kg body weight for 35 days significantly enhanced nocturnal spontaneous locomotor activity, with the 1.2 g/kg body weight dose (equivalent to 0.144 g/kg body weight in humans) reducing damages of extensor digitorum longus muscle by nearly 50%. Although consecutive forced exercises, specifically horizontal and downhill treadmill running, reduced GlcNAc-mediated improvement, mice treated with 0.6 and 1.2 g/kg body weight still showed increased overall spontaneous locomotor activity under this condition, despite the lack of protection against repeated eccentric contraction-induced injury. These findings suggest that GlcNAc enhances overall muscle health, possibly through mechanisms other than direct protection from muscle injury. One possible contributing mechanism may involve enhanced muscle repair or regeneration, as suggested by our related in vitro myogenesis work. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly prescribed for DMD patients, further enhanced spontaneous locomotor improvement in mdx mice compared to prednisolone alone. These findings suggest that GlcNAc has the potential to improve the clinical status of DMD patients, either as a monotherapy or in combination with corticosteroids.