Biology of Lipids in the Control of the Motor Function, in Health and Diseases

Voluntary movements are tightly controlled by different populations of neurons located in the central and peripheral nervous systems. The electric impulses that initiate the voluntary movements originate from layer V of the motor cortex and propagate via the pyramidal tracts to bulbar and spinal alpha motor neurons, which in turn, trigger muscle contractions. Other structures, such as the reticular formations, the cerebellum and the striatum, are implicated in the balance and coordination of motor functions.

Lipids are various molecules acting as i) energy nutrients, ii) key membrane components or iii) signalling molecules with key molecular functions. The nervous system is enriched in complex lipids, such as sphingolipids. They participate directly in the maturation of axons from the pyramidal and extra-pyramidal tracts. The loss of these complex lipids impairs electric impulse transmission, which leads to impaired neuronal functions. Lipids and their derivatives regulate cell signalling by acting as ligands or, if present at the cell membrane, they interact with the receptors of trophic factors. At the extremity of the motor units, the activity of skeletal muscles also depends on large energy supplies provided by lipids. Moreover, the presence of cholesterol and complex lipids is crucial for the integrity of neuromuscular junctions and the clustering of acetylcholine receptors.

Recent studies connect dysregulations in lipid metabolism to a broad range of neurological disorders with motor dysfunctions. In amyotrophic lateral sclerosis, the deregulation of the CNS and the muscle lipid metabolisms has direct repercussions on neuronal signalling, muscle innervation, and energy metabolism. In addition, changes in the synthesis, distribution or degradation of lipids, such as sphingolipids or cholesterol, have been detected in the spinal cord of some forms of hereditary spastic paraplegia, in the substantia nigra of Parkinson’s disease and these changes can trigger epileptic seizures potentially affecting the control of motor functions. Lipids present in the myelin sheaths are at the centre of pathological processes in the Guillain-Barré syndrome and potentially in the neurological symptoms following an infection by Zika virus.

The practice of physical activity tunes the nutrient preference of muscle fibres, and therefore on mitochondrial activity and beta-oxidation of fatty acids. Importantly, recent studies suggest that the plasticity of muscle energy metabolism may have an influence on the physiology and biomolecular properties of spinal motor neurons.

This Research Topic will explore the role of lipids in the molecular mechanisms underlying the cellular control and integrity of motor functions. We welcome the submission of original research articles and reviews to provide a better picture of the contribution of lipids to the motor system, in health and in all diseases with a defect in motor functions.