SENSORIMOTOR RESTRICTION DURING DEVELOPMENT INDUCES MITOCHONDRIAL ALTERATION WITHIN MUSCLE AND BRAIN STRUCTURES

Physical inactivity and sedentary lifestyle during childhood can lead to musculoskeletal and motor deficits but also cognitive and behavioral disorders. Most children with developmental coordination disorders or autism spectrum disorders show sensorimotor impairments, reduced physical activity, altered interactions with their environment and atypical motor development. Since ATP produced by mitochondria is essential for muscle contraction, neurotransmission, and brain plasticity processes, emerging hypotheses suggest that functional alterations could be related to energy metabolism. Understanding the mechanisms behind these neurodevelopmental deficits is a prerequisite for developing remediation strategies, and the later are crucial to promote self-reliance and independence, to improve future quality of life and to decrease the risk of neurodegenerative diseases during ageing. In order to better understand the emergence of neuromuscular or cognitive disorders during childhood, a model of early sensorimotor restriction was developed in rats. It consists in casting pups’ hindlimbs from birth to postnatal day 28 (P28). These animals display a prominent motor phenotype that includes muscle weakness, locomotor disturbances and altered cognitive and executive functions. Our aim was to determined whether early sensorimotor restriction alters mitochondrial metabolism in rat muscles and brain structures. Enzyme activities of citrate synthase and respiratory chain complexes I, II, and IV were measured using a spectrophotometric technique in two hind limb muscles (soleus and extensor digitorum longus) and several brain structures (hippocampus, prefrontal cortex, striatum, cerebellum and sensorimotor cortex) in control rats and rats experiencing early sensorimotor restriction at P15 and P28. Our results show a decrease in mitochondrial enzyme activities in the soleus, in the extensor digitorum longus, and in the hippocampus, while no effect was observed in other brain structures. To sum up, the effect of early sensorimotor restriction on mitochondrial metabolism is structure-dependent, structures involved in cognitive functions being more affected than those involved in motor processes.