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 whose intracellular concentration is closely associated with 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-to-cell and cell-to-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, augments muscle regeneration in vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in a murine model of Duchenne muscular dystrophy (DMD) (mdx mice). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Administering GlcNAc at concentrations of 0.6, 1.2, 1.8, and 2.4 g/kg body weight per day for 35 days significantly improved nocturnal spontaneous locomotor activity at all those doses, with the 1.2 g/kg body weight dose reducing damages of extensor digitorum longus muscle by nearly 50%. While consecutive forced exercises, including horizontal and downhill treadmill running, reduced GlcNAc-promoted locomotor activity, treatment with 0.6 and 1.2 g/kg body weight treatment results in increased spontaneous locomotor activity. These results suggest that GlcNAc enhances overall muscle health, likely through promoting muscle repair/regeneration rather than preventing damage formation. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly used in 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.