Effects of low-intensity training on the brain and muscle in the congenital muscular dystrophy 1D model.

INTRODUCTION: Congenital Muscular Dystrophy type 1D (MDC1D) is characterized by a hypoglycosylation of α-dystroglycan protein (α-DG), and this may be strongly implicated in increased skeletal muscle tissue degeneration and abnormal brain development, leading to cognitive impairment. However, the pathophysiology of brain involvement is still unclear. Low-intensity exercise training (LIET) is known to contribute to decreased muscle degeneration in animal models of other forms of progressive muscular dystrophies. AIM: The objective of this study was to analyze the effects of LIET on cognitive involvement and oxidative stress in brain tissue and gastrocnemius muscle. METHODS: Male homozygous (Largemyd-/-), heterozygous (Largemyd+/-), and wild-type mice were used. To complete 28 days of life, they were subjected to a low-intensity exercise training (LIET) for 8 weeks. After the last day of training, 24 h were expected when the animals were submitted to inhibitory avoidance and open-field test. The striatum, prefrontal cortex, hippocampus, cortex, and gastrocnemius were collected for evaluation of protein carbonylation, lipid peroxidation, and catalase and superoxide dismutase activity. RESULTS: LIET was observed to reverse the alteration in aversive and habituation memory. Increased protein carbonylation in the striatum, prefrontal cortex, and hippocampus and lipid peroxidation in the prefrontal cortex and hippocampus were also reversed by LIET. In the evaluation of the antioxidant activity, LIET increased catalase activity in the hippocampus and cortex. In the gastrocnemius, LIET decreased the protein carbonylation and lipid peroxidation and increased catalase and superoxide dismutase activity. CONCLUSION: In conclusion, it can be inferred that LIET for 8 weeks was able to reverse the cognitive damage and oxidative stress in brain tissue and gastrocnemius muscle in MDC1D animals.

Behavioral Responses in Animal Model of Congenital Muscular Dystrophy 1D.

Congenital muscular dystrophies 1D (CMD1D) present a mutation on the LARGE gene and are characterized by an abnormal glycosylation of α-dystroglycan (α-DG), strongly implicated as having a causative role in the development of central nervous system abnormalities such as cognitive impairment seen in patients. However, in the animal model of CMD1D, the brain involvement remains unclear. Therefore, the objective of this study is to evaluate the cognitive involvement in the Large(myd) mice. To this aim, we used adult homozygous, heterozygous, and wild-type mice. The mice underwent six behavioral tasks: habituation to an open field, step-down inhibitory avoidance, continuous multiple trials step-down inhibitory avoidance task, object recognition, elevated plus-maze, and forced swimming test. It was observed that Large(myd) individuals presented deficits on the habituation to the open field, step down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance, object recognition, and forced swimming. This study shows the first evidence that abnormal glycosylation of α-DG may be affecting memory storage and restoring process in an animal model of CMD1D.