• Science Saturday: Explaining cholesterol, research and regeneration

Isobel Scarisbrick, Ph.D., directs the Neural Repair Laboratory within Mayo Clinic's Department of Physical Medicine and Rehabilitation. Her lab examines central nervous system repair after injury, such as traumatic spinal cord injury or a disease like multiple sclerosis (MS). A major area of innovation for the lab is improving nerve regeneration by identifying what helps or hinders that process.

Cholesterol, the yellow bilayer shown at left, is vital to the body. It is a key component of cell membranes for structure and flexibility. Cholesterol helps insulate axons as part of a neuron's myelin sheath. Cholesterol is a precursor for synthesis of vitamin D and some hormones (steroid/sex), and it's part of bile salt used in digestion. Cholesterol can be synthesized by cells, and is created by the body in the liver and brain.

Mayo Clinic's Center for Regenerative Medicine supports Dr. Scarisbrick's research as part of its objective of advancing research aimed at bringing new cures to the practice. Dr. Scarisbrick also serves as program director for the Regenerative Sciences Track within the Ph.D. Program of Mayo Clinic Graduate School of Biomedical Sciences, which was developed in collaboration with the Center for Regenerative Medicine.

Since the late 1990s, Dr. Scarisbrick has traced the body's mechanisms for repair. In 2013, she and a team of authors reported that kallikrein 6, an enzyme linked to neurodegeneration, in concert with the enzyme thrombin, linked to blood clotting. These enzymes were elevated in mouse models of spinal cord injury and shown to contribute to neurodegeneration. They acted via two receptors called PAR1 and PAR2.

Regenerative Medicine Minnesota recognized Dr. Scarisbrick's innovative work in regeneration for chronic spinal cord injury by awarding funding to advance her research. This statewide bipartisan initiative makes grants to advance regenerative medicine research and technology.

The team extended its finding in models of MS and a type of brain cancer. Over the past six years or so, the team clarified further effects of these enzymes and receptors. The scientists have examined not only neural cells, but also the enzyme and receptor effects on the immune system and cellular microenvironments.

Last year, they pivoted to look at diet, publishing two papers on how a high-fat diet affects the central nervous system. This year, they've narrowed the focus to cholesterol and its contribution to repair of tissues after spinal cord injury. Dr. Scarisbrick explains below.

Cholesterol, research and regeneration

"Aside from injury, systemic metabolic dysfunction itself also impairs the innate capacity for repair and regeneration in general. We haven't published all the data yet, and this work by the way was funded by the Center for Biomedical Discovery, but I call the oligodendrocytes — those little glial cells that produce the myelin sheath to insulate neurons — I call them the canary in the coal mine. They are very sensitive to diet.

We are looking at the high-fat/high-sucrose diet, a high-fat diet, and now a low- carb/high-fat diet. Basically, it's looking like anything extreme is not good for the oligodendrocytes and the myelin sheath.

Read the rest of the article on the Center for Regenerative Medicine blog.


Other Mayo Clinic medical research websites:

Related articles