Early sensorimotor restriction in rats induces age-dependent mitochondrial alterations in skeletal muscles and brain structures

Abstract

A sedentary lifestyle can lead to motor and cognitive deficits, increasing the risk of neurodegenerative diseases in ageing. Emerging hypotheses suggest that these functional alterations may be related to energy metabolism. Indeed, ATP produced by mitochondria is essential for muscle contraction, neurotransmission and brain plasticity processes. Although a sedentary lifestyle has been associated with mitochondrial alterations in skeletal muscle, the potential effects on brain structures have yet to be investigated. The present study aimed to determine whether early sensorimotor restriction (SMR) alters mitochondrial metabolism in rat muscles and brain structures. Enzyme activities of citrate synthase (CS) and respiratory chain complexes I, II and IV were measured using a spectrophotometric technique and mitochondrial respiration was assessed using high-resolution respirometry in two hind limb muscles [soleus and extensor digitorum longus (EDL)] and four brain structures (sensorimotor cortex, striatum, prefrontal cortex and hippocampus) in control rats and rats experiencing early SMR from birth to day 28. Mitochondrial enzyme activities decreased in the soleus (complexes I and II), in the EDL (complex I) and in the hippocampus (complexes I and IV) in an age-dependent manner, whereas no effect was observed in other brain structures. CS activity decreases in the soleus and increases transiently in the striatum and sensorimotor cortex at postnatal day 15. Mitochondrial respiration was reduced in the soleus and in the sensorimotor cortex (CI and CI+CII). Early SMR appears to induce quantitative and qualitative mitochondrial alterations in skeletal muscles and certain brain structures involved in cognitive and motor processes.

Key points

• Early sensorimotor restriction (SMR) alters mitochondrial enzyme activities and mitochondrial respiration in skeletal muscles and brain.
• Mitochondrial alterations induced by early SMR are age-dependent, structure-dependent and complex-dependent.
• Mitochondrial enzyme activities increase during development and the evolution pattern is specific to the different structures.