Targeting Myelin Metabolism to Enhance Recovery of Function After Spinal Cord Injury

Diet is an intrinsic aspect of everyday life and is emerging as a major regulator of brain function and plasticity. In particular, the increasing consumption of saturated fats and sugars in a typical Western diet is considered detrimental for central nervous system function; however, based on the high content of lipids in the brain, how to manage consumption of dietary fats for optimal CNS health is controversial. Myelin is essential to the conduction of nerve impulses in the brain and spinal cord and myelin loss is a key pathophysiological component of neurological injury and disease, including multiple sclerosis, traumatic brain and spinal cord injury, stroke and certain neuropsychiatric disorders. Myelin membranes have a very high lipid-to-protein ratio, in which lipids account for at least 70 percent of the dry weight. Myelin assembly therefore requires an extraordinary amount of lipids, especially lipids such as cholesterol and fatty acids that are enriched in myelin.

Recent findings from Dr. Scarisbrick's lab suggest for the first time that consumption of a diet high in saturated fats and sugar compromises the health of myelinating cells. However, the research team demonstrated these deleterious effects are completely reversed by co-ordinate exercise training, as cited in BBA Molecular Basis of Disease, 2016 (Yoon et al.). These new studies suggest that the central nervous system is capable of adapting to the demands of a high-energy Western diet, coupled with ample exercise, by increasing insulin like growth factor 1 (IGF-1) signaling and the expression of silent mating type information regulation 2 homolog (SIRT1), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), and free radical scavengers. In the absence of exercise, however, a high fat consumption results in increases in reactive oxygen species without coordinate elevations in SIRT1 and may lead to myelin degeneration.

The central hypothesis being tested by Dr. Scarisbrick's research team is that diet and exercise induced changes in critical regulators of metabolism, such as IGF-1 SIRT1, PGC-1α and free radical scavengers regulate the capacity of the nervous system to generate and repair myelin. The team is exploring whether exercise or metabolic regulators or both can be targeted therapeutically to enhance myelin regeneration to achieve improved patient functional outcomes.

These studies have important implications for the design of rehabilitative programs to enhance functional capacity in the brain and spinal cord by promoting myelin formation and regeneration with both dietary fat content and exercise being essential considerations.

This research is funded by the Mayo Clinic Rehabilitation Medicine Research Center, the Mayo Clinic Center for Regenerative Biotherapeutics and the Mayo Clinic Metabolomics Resource Core Pilot and Feasibility Program award.