Oct. 11, 2016
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 some neuropsychiatric disorders.
Identifying factors that encourage production of and protect the function of myelin-producing cells — oligodendrocytes and their progenitors (OPCs) — is an important avenue of research aimed at promoting central nervous system (CNS) health.
In a recently published article in Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease, Isobel A. Scarisbrick, Ph.D., director of the Neuroregeneration and Neurorehabilitation Laboratory at Mayo Clinic's campus in Rochester, Minnesota, and co-authors investigate the relationship between fat intake, exercise and myelin production in mice.
The roles that dietary fat intake and other external factors play in the production of oligodendrocytes and OPCs is not well-understood. Although brain lipids have high fat content, consumption of a diet containing excess fats and sugars has been shown to be detrimental to CNS function. However, myelin assembly requires a significant amount of lipids, and lipids play an important role in glial cell myelination.
Exercise has been shown to have positive effects on CNS function. Recent research has yielded evidence that exercise can modulate the action of diet on the CNS. Additional animal and human studies have shown that new myelin formation in the brain is required to learn new skills, whether it's running on an exercise wheel or learning to play the piano or juggle.
"Our study was designed to provide a clearer picture of the interaction between high fat consumption and exercise training and their effect on myelin and myelin-forming cells in the adult spinal cord," explains Dr. Scarisbrick.
Mayo researchers studied adult mice, randomized into four experimental groups: Two groups had a sedentary lifestyle and free access to a regular diet (SRD) or a high-fat diet (SHF). Another two groups were assigned to either the regular diet (ERD) or the high-fat diet (EHF) and had free access to an exercise running wheel.
Myelin-producing oligodendrocyte stained immunochemically for sulfatide (green). Blue area is DAPI-stained nuclei.
Dietary fat, exercise and myelin dynamics
Hypothetical model by which dietary fat and exercise influence myelin dynamics in the adult spinal cord. 1. Dietary fat may serve as a source of myelin membrane precursors, including fatty acids and cholesterol. 2. Data presented suggest that high fat consumption on its own, or in combination with exercise, can increase IGF-1 and pro-myelinogenic signaling pathways such as AKT. 3. The interactive actions of exercise and high fat may also serve to regulate pathways associated with energy homeostasis involving mitochondrial function. Image reprinted with permission from Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease.
After seven weeks, researchers analyzed the lumbosacral spinal cord tissue to measure the effects of diet and exercise on several building blocks required for myelin assembly in the four study groups, including proteolipid protein (PLP) and myelin basic protein (MBP).
- High-fat diet in combination with exercise training increases myelin protein expression. PLP and MBP levels were highest in the group that exercised and consumed a high-fat diet. Exercise training or high fat consumption alone also increased PLP. MBP levels in the ERD and the SHF groups were not significantly different.
- High-fat diet alone or in combination with exercise has the greatest effect on myelin-related protein expression. The SHF and EHF groups had the highest levels of PLP RNA. Elevations in PLP RNA induced by a high-fat diet alone (SHF) were significantly greater than those achieved by exercise training alone (ERD).
- Exercise training protects against loss of OPCs or mature oligodendrocytes induced by a high-fat diet. The SHF group had 30 to 50 percent fewer OPCs. While exercise alone didn't affect the OPC or oligodendrocyte numbers, mice in the EHF group did not experience OPC loss.
- Exercise training in combination with a high-fat diet positively modulates expression of IGF-I levels. This growth factor is known to play important roles in OPC proliferation, survival and differentiation. IGF-1 RNA levels were highest in the ERD and EHF groups, suggesting that exercise exerts the greatest influence here.
- High-fat diet in combination with exercise converges on energy biosensing systems to restore mitochondrial function and free radical homeostasis. While SHF mice experienced excessive mitochondrial activity and free radical production, EHF mice upregulated silent mating type information training (SIRT1) and the production of free radical scavengers that may protect myelin and myelinating cells from damage in the central nervous system.
These findings suggest that the central nervous system is capable of adapting to the demands of a high-energy Western diet when afforded ample exercise.
"Our results suggest that consuming high levels of saturated fat in conjunction with a sedentary lifestyle can lead to a reduction in myelin-forming cells. But exercise training can help reverse this process and promote the myelinogenesis necessary to meet increased energy demands," explains Dr. Scarisbrick.
For more information
Yoon H, et al. Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system. Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease. 2016;1862:545.