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Running May Help Repair Some Types of Brain Damage

Aerobic exercise triggers production of a molecule that repairs the cerebellum.

Wikimedia Common/Public Domain
This early anatomical sketch of the cerebellum highlights the arbor vitae (Latin for "tree of life") because of its branched, tree-like appearance. The arbor vitae houses the white matter of the cerebellum, which facilitates communication between the gray matter in various regions throughout the brain
Source: Wikimedia Common/Public Domain

Canadian researchers have discovered that running triggers the release of a specific molecule—VGF nerve growth factor—which helps mice repair specific types of brain damage. Their findings were published yesterday in the October 2016 journal Cell Reports.

This cutting-edge discovery, by a team of researchers from The Ottawa Hospital and the University of Ottawa led by David Picketts, adds to a growing list of neuroprotective benefits derived from aerobic exercise. If you need one more reason to motivate yourself to exercise, hopefully, knowing that physical activity improves brain health—while combating depression and anxiety—will inspire you to move more and sit less on a daily basis.

Previous research has found that physical exercise significantly increases VGF production in specific brain regions and triggers a chain reaction that is potentially linked to the efficacy of antidepressants. VGF is also believed to have an endogenous antidepressant effect associated with runner’s high. VGF helps make you feel good anytime you break a sweat while working out.

Life Science Databases/Wikimedia Common
Cerebrum (Latin for "brain") in red.
Source: Life Science Databases/Wikimedia Common

In their recent study, the Canadian researchers found that VGF nerve growth factor also helps to heal the protective myelin coating that surrounds and insulates nerve fibers in the cerebellum.

Gray matter (sometimes spelled grey matter) consists of unmyelinated neurons throughout the cerebrum, brainstem, and cerebellum; it is also present throughout the spinal cord. White matter is named for its lighter appearance caused by the lipid content of the insulating myelin sheaths that speed up communication between various brain regions.

Picketts’ laboratory focuses on researching the role of various proteins in neural development and intellectual disability disorders. They utilize transgenic mouse models in which genes encoding epigenetic regulators are genetically inactivated to identify their requirement during brain development. This helps them pinpoint the brain mechanisms that might be causing intellectual or physical disability.

Life Science Databases/Wikimedia Common
Cerebellum (Latin for "little brain") in red.
Source: Life Science Databases/Wikimedia Common

For their latest study, Picketts et al. were using a strain of mice who had been genetically modified to have a small cerebellum. Due to the shrunken size of their cerebellum, these mice suffered from ataxia and had trouble walking or moving with fluidity. Typically, the mice with smaller cerebellums only lived for about 25 to 40 days. But, if these mice were given the opportunity to voluntarily run on a wheel, their lifespan was extended to more than 365 days.

The researchers believe this discovery could pave the way for new treatments for multiple sclerosis (MS) and other neurodegenerative disorders that involve damaged nerve insulation. MS is marked by a complex immune-mediated process in which an abnormal response of the body’s immune system targets myelin and destroys fatty substance around each nerve fiber that provides insulation and optimal brain communication.

Damaged myelin creates scar tissue which is called “sclerosis.” When any part of the myelin sheath is damaged or destroyed it interrupts the nerve impulses traveling throughout the brain and disrupts the communication lines of white matter tracts between various brain regions.

In a statement to the University of Ottawa, David Picketts said, "We are excited by this discovery and now plan to uncover the molecular pathway that is responsible for the observed benefits of VGF. What is clear is that VGF is important to kick-start healing in damaged areas of the brain."

VGF Helps Facilitate the Neuroprotective Powers of Exercise

Historically, the cerebellum has been thought of by most experts as solely a ‘non-thinking’ brain center responsible for fine-tuning muscle movements and controlling balance. However, a growing body of research implies that the cerebellum may, in fact, play an important role in cognitive function or the degeneration of executive function and memory.

As an example, last week, researchers at Harvard Medical School, reported that atrophy of subcortical brain regions including the cerebellum were indicative of a combination of reductions in gray matter brain volume associated with cognitive deficits in Alzheimer’s disease.

The mice in the recent Canadian study who ran voluntarily acquired a better sense of balance compared to their sedentary counterparts. Their ataxia also improved. This caused the researchers to dig deeper into what was going on in the cerebellum. Upon closer inspection, the researchers identified that the running mice had gained significantly more myelin insulation around the white matter nerve fibers within their cerebellum.

To pinpoint why running was causing the growth of healthier myelin sheaths, the team looked for differences in gene expression between the running and sedentary mice. This is when they identified VGF as the prime candidate for improving myelin insulation via a process called “VGF-mediated oligodendrogenesis.” VGF is one of hundreds of molecules (including irisin) that muscles release into the body and brain during exercise.

When the research team used a non-replicating virus to introduce the VGF protein into the bloodstream of a sedentary mutant mouse, the effects mimicked those of the mice who were running consistently. Triggering the production of VGF led to more insulation in the damaged area of the cerebellum and fewer disease symptoms. This discovery could lead to revolutionary treatments for neurodegenerative diseases in the future.

In a classic example of “use it or lose it,” the mice needed to keep exercising in order to maintain the neuroprotective benefits of VGF. Unfortunately, if their running wheel was removed from the cage, their symptoms came back and they would die sooner.

In his statement, David Picketts concludes, “We need to do broader research to see whether this molecule can also be helpful in treating multiple sclerosis and other neurodegenerative diseases.”

The “Little Brain” Could Take Center Stage in the Twenty-First Century

This new study on running mice overcoming ataxia by bulking up the white fiber tracts in the cerebellum offers many clues that might apply to other mammals, including humans. For example, Jeremy Schmahmann, who heads the Massachusetts General Hospital ataxia unit at Harvard Medical School, has spent his career studying the neurological and psychological ramifications of damage to the cerebellum in human patients with ataxia.

Schmahmann has a radical theory, Dysmetria of Thought, which is the hypothesis that the cerebellum fine-tunes cognitive processes in the left and right hemispheres much the same way it fine-tunes muscle movements via the motor cortex in the cerebral cortex—which plans and controls the execution of voluntary movements.

Photo and illustration by Christopher Bergland (Circa 2009)
This rudimentary "Super 8" sketch illustrates how optimizing the functional connectivity of white matter tracts within and between all four brain hemispheres might foster a state of "superfluidity."
Source: Photo and illustration by Christopher Bergland (Circa 2009)

As someone who loves to run, bike, and swim, I’ve always noticed that engaging in aerobic activity helps to clarify my thoughts, problem solve, come up with fresh ideas, and connect the dots in new and useful ways. For decades, I’ve been on a mission to isolate the brain mechanics that explain the link between aerobic activity, creative thinking, and the increased likelihood of having a Eureka! moment.

One clue towards solving this riddle came in June 2016, when a study on creativity by Manish Saggar of Stanford University was published in Cerebral Cortex. Saggar and his colleagues found that increased connectivity between the cerebrum and cerebellum boosts creative capacity. Other studies have found that aerobic exercise optimizes white matter connectivity across the corpus callosum between the left and right hemispheres of the cerebrum.

Although it's speculative on my part, when I first read the new study from Picketts’ lab this morning, I had a mini Aha! moment and asked myself: "Maybe triggering the production of VGF via aerobic exercise can help optimize the functional connectivity of white matter tracts in the cerebellum for people from all walks of life?"

An uptick of VGF could help create a state of superfluidity which is a term I borrowed from the world of physics to describe the feeling of your body, mind, and brain operating with absolutely zero friction or viscosity. Again, this hypothesis is just an educated guess at this point. Stay tuned for more scientific discoveries on this exciting topic!

© 2016 Christopher Bergland. All rights reserved.

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