| Abstract: | Background Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the lethal disease. Previous studies reported potent efficacy of DL-NBP for several neurodegenerative disorders and cerebral ischemia. In this study,we investigated the efficacy of DL-NBP on ALS model mice.Methods Sixty SOD1-G93A female mice were divided into four groups: vehicle control, 30mg, 60mg, and 120mg DL-NBP/kg. For measurement of motor activity, Hanging wire test and Rotarod test were performed and survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice one week. The statistical motor unit number estimation (MUNE) technique was used to estimate the number of functioning motor units in gastrocnemius muscle.Musle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantitation was performed by Nissl staining and microglia activation was observed by immunohistochemistry.Results Oral administration of 60 mg/kg DL-NBP significantly prolonged survival (164.78±16.672 days) compared to vehicle control(140.00±16.892 days). 60mg/kg DL-NBP treatment significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that 60mg/kg DL-NBP slowed the rate of MUNE reduction (p<0.01).Motor neurons were remarkably preserved in the anterior horns in mice treated with 60mg/kg DL-NBP at the stage of 19 weeks, (p<0.01). 60mg/kg DL-NBP treatment significantly reduced CD11b immunoreactivity compared with vehicle control mice (p<0.05). No significant effect was observed in 30mg/kg and 120mg/kg DL-NBP-treament.Conclusions The post-onset administration of DL-NBP significantly prolonged survival and improved motor performance in SOD1-G93A mice. DL-NBP may be a potential therapeutic agent for ALS. |
