“Turbocharging” the brain
By now, most people are familiar with the concept of blood doping, which is the misuse of specific techniques and/or substances to increase one’s red blood cell mass. This, in turn, allows the body to transport more oxygen to muscles, thus improving stamina and performance. Blood doping can also involve training at high altitudes and storing the blood until needed for a competition at lower altitudes or sea level. But what if the blood from an athlete could enhance brainpower in another person, especially a person who doesn’t or can’t exercise? What if a protein that gets amplified when someone exercises could help prevent Alzheimer’s and other memory disorders? A new study published in the journal “Nature” found that sedentary mice did better on learning and memory tests after being injected with the blood from mice that ran for miles on exercise wheels. The study also found that once the mice had received blood from more athletic mice, the type of brain inflammation involved in Alzheimer’s and other neurological disorders was reduced. Granted, mice and men aren’t quite the same thing, but scientists believe this warrants more research.
“We’re seeing an increasing number of studies where proteins from outside the brain that are made when you exercise get into the brain and are helpful for improving brain health, or even improving cognition and disease,” according to Rudolph Tanzi, a professor of neurology at Massachusetts General Hospital and Harvard Medical School, who led a 2018 study into the ability of exercise to help the brains of mice engineered to have a version of Alzheimer’s. Researchers are hoping to find out whether “exercise-generated” proteins, such as clusterin, which is produced in liver and heart muscles cells, could lead to a treatment for this debilitating disease. Dr. Madhav Thambisetty, a neurologist at the National Institute on Aging, says, “The demonstration that there are transferable factors in the blood that seemed to convey beneficial effects on the brain that improve learning and memory is by far the most interesting aspect of the work.” Thambisetty believes it’s far too early to determine whether high or low clusterin levels will provide anti-inflammatory benefits as more research is needed. Still, the researchers noted that when clusterin was removed, the anti-inflammatory effects disappeared. Conversely, when mice with engineered brain inflammation or a version of Alzheimer’s were injected with clusterin, it reduced inflammation in their brains. Clusterin binds to cells in the brain that line the blood vessels, and it’s these cells that become inflamed in Alzheimer’s disease.
The study, led by Tony Wyss-Coray, professor of neurology and neurological sciences at Stanford, involved mice who could use exercise wheels as much as they wanted and mice who couldn’t use the wheel because it was locked. The idea was to see if factors produced by exercise would collect in the blood and then be transferred to other mice. Each night, the runner mice clocked about four to six miles on the wheel. “After 28 days, the researchers took a third group of mice that also did not exercise and injected them with blood plasma, the liquid that surrounds blood cells, from either the runner mice or the non-runner mice. Mice receiving runner blood did better on two tests of learning and memory than those receiving blood from the non-runner mice,” according to the researchers. They also discovered that the brains of mice that had been injected with runner blood produced “more of several types of brain cells, including those that generate new neurons in the hippocampus, a region involved in memory and spatial learning.”
The only people involved in the study were 20 military veterans ranging in age from 50 to 89 who exhibited mild cognitive impairment. After participating in a six-month program where they exercised three times weekly, combining weight training and cardio, all participants showed high clusterin levels in their blood. Moreover, they performed better on vocabulary memory and story recall. “Across the board, veterans had improvements in cognitive function, largely related to learning and memory,” according to Dr. Kaci Fairchild, associate director of the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center. Dr. Fairchild hopes that “the implications from this clusterin is that we can develop a medication targeting this protein for persons who weren’t able to engage in physical activity.”
More research needed
Experts studying Alzheimer’s disease and neuroinflammation believe more research is needed. “Not everything that works in mice works in humans, and we don’t know if there are other unexpected side effects that could make it untenable in humans,” said Mark Gluck, a professor of neuroscience and public health at Rutgers University who was not involved in the study. Moreover, inflammation’s role in disease may change over time, so it’s crucial to target inflammation at just the right time. Researchers are unclear if clusterin is the best protein for therapy, as irisin and Gpld1 have also shown improvement in cognition. So, the big question for researchers is which proteins will be the winners, and how can we take advantage of them to provide new therapies.” Regardless of which protein comes out on top, it’s cutting-edge research like this that could lead to “turbocharging” the brain and preventing Alzheimer’s.