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Weight Lifting Overcomes Cognitive Impairment in Rats

Exercise-Produced Lactic Acid Linked to Brain Adaptation

Last month we promised more details on the improved brain function in weight-trained rats. Turns out that the underpinnings of the exercise-brain connection are substantial.

Let’s start with the proven role of lactic acid, or lactate, a chemical byproduct of high intensity exercise. I wrote about it in Physiological Factors (2006).

New Thinking on Lactic Acid

Setting the stage: You’ve probably heard that lactic acid is a waste product that burns and shuts down muscles, and makes you sore a day or so later. It’s something athletes and fitness exercisers are urged to avoid. You’re told to work out just below your lactate threshold, where lactic acid begins to accumulate. That’s mostly wrong. Scientists have discovered that lactic acid is an important fuel, central to carbohydrate metabolism. Unfortunately, if you don’t train properly, it can also impair performance. Your goal should be to burn lactic acid more effectively, not produce less of it.

Key details: The old lactic acid theory is based on an experiment performed on dissected frog legs. I remember hearing about it in biology class. After being subjected to electric shock, the frog legs contracted a few times and then stopped working. The motionless frog legs were found to be saturated with lactic acid.

Voila! Lactic acid is bad; it brings muscles to a halt.

“It was one of the classic mistakes in the history of science,” UC Berkley integrative biology professor George A. Brooks explained. “I gave [lab] rats radioactive lactic acid, and I found that they burned it faster than anything else I could give them.”

Dr. Brooks concluded that lactic acid is an important source of energy—and later research has proven him to be correct.

Thomas D. Fahey, Ed.D, Professor of Exercise Physiology at California State University at Chico, filled in more of the details on the new findings. “Dr. George Brooks describes the dynamic production and use of lactic acid in metabolism in his Lactate Shuttle Theory. This theory describes the central role of lactic acid in carbohydrate metabolism and its importance as a fuel,” Fahey explained. “The heart, slow-twitch muscle fibers, and breathing muscles [actually] prefer lactate as a fuel during exercise.”

Establishing lactic acid as a link: “[The below] experiment is the clincher, proving that lactate is the link between glycolytic [anaerobic] metabolism, which breaks down carbohydrates, and oxidative metabolism, which uses oxygen to break down various fuels,” Brooks said.

Post-doctoral researcher Takeshi Hashimoto and staff research associate Rajaa Hussien made the actual discovery. (Forgive the technical jargon; you’ll get the idea.) The researchers located and labeled “three critical pieces of the lactate pathway: the lactate transporter protein; the enzyme which catalyzes the first step in the conversion of lactate into energy; and the protein complex where oxygen is used. Peering at skeletal muscle cells through a microscope, the two scientists saw these proteins sitting together inside the mitochondria, attached to the mitochondrial membrane, proving that the intracellular lactate shuttle is directly connected to the enzymes in the mitochondria that burn lactate with oxygen.”

Brooks says that these finding “can help athletes and trainers design training regimens. Athletes may instinctively train in a way that builds up mitochondria, but if you never know the mechanism, you never know whether what you do is the right thing.”

Knowledgeable coaches recommend a combination of high intensity and endurance training “to improve the capacity to use lactic acid as a fuel during exercise and recovery.” Both forms of training increase and improve the mitochondria.

Wherever you fall on the endurance-strength continuum, remember that lactic acid is a fuel, not a poison.  

You can read the rest of the article, including more detailed advice on training: https://www.cbass.com/Lacticacid.htm

*  *  *

Let’s move on to a study which lays the groundwork for weight-training rats.

Exercise-Generated Lactate in Mice Produces Brain Changes

Researchers from the University of Kansas Medical Center, led by E. Lezi (Alzheimer’s Disease Center), focused on lactate’s ability to facilitate changes in brain function, and reported their findings online August 26, 2013, in the Journal of Neurochemisty.

“It was recently postulated that physical exercise might potentially delay or mitigate agerelated central nervous system diseases such as Alzheimer's disease, perhaps through effects on brain [function],” Lezi et al wrote in introducing their study. “Lactate, which is generated and released by exercising muscle, in particular appears to affect the brain.”

For these reasons and others, they exercised mice intensely to gain a better understanding of lactate’s impacts on brain function.

In one group of experiments, mice underwent 7 weeks of treadmill exercise sessions at intensities intended to exceed the lactate threshold. Over time, the mice dramatically increased their lactate threshold. To ensure that plasma lactate accumulated during the final week, the mice were run to exhaustion.

The technical details are beyond my knowledge level. Not aimed at layman, like me.

Simply put, they found that high-intensity exercise in mice, sufficient to elevate blood lactate levels, produces changes in the brain.

An Editorial Highlight, published along with the study, relates the findings in language we can understand:

“The case for exercise in brain health is continuing to deepen to the point where it seems the weight room is as critical for brain function as it is for building muscle mass. Increased cardiovascular function, improved psychological profile, increased neurotrophic factors, and neurogenesis are but a few of the factors linked to the benefits of vigorous exercise. A mechanistic understanding of how exercise can bring about such [multiple] range of changes has remained elusive prior to the study by Swerdlow and colleagues published in this issue of Journal of Neurochemistry (Lezi et al. 2013). Insightfully, these investigators used the most elementary product of exercise physiology, lactate, to mimic exercise. The authors found that lactate administered to resting mice produced many of the same benefits to brain mitochondria density found during extensive exercise.”

* *  *

Now, we’re ready to assess the study of weight trained rats; it ain't no joke. The focus is on brain cell creation and repair rather than lactate.

Gym Rats Show Path to Brain Health

As detailed last month and here, research has found a link between high-intensity exercise and brain health. Taylor J. Kelty and colleagues at the University of Missouri have gone a step further and mapped out the molecular signaling process that connects resistance training to improved cognitive function and memory. In their study published online in the Journal of Applied Physiology on July 15, 2019, they demonstrated that weight training can overcome cognitive impairment and repair or create neurons, the basic working units of the brain.

Using rats, three resistance-training “workouts” a week for 6 weeks improved cognition and boosted memory performance.

To discover these molecular changes, the researchers first needed rats with cognitive impairment, which they achieved by injecting a type of fat that inflamed their neurons.

Since it’s difficult to persuade rats to lift weights—especially rats who are cognitively impaired—the researchers attached small weights to their hindquarters and trained them to climb a 3-foot high ladder. Doing several sets of this a few times a day, 3 days a week, had the effect of strength training. Soon, the rats were building muscles. As their strength increased, they were loaded with progressively heavier weights.

Another group of rats (the sedentary group) also had induced cognitive impairment, but did no lifting. A third group of rats (the control group) had fake training but weren’t given the fat injection to the brain, so they weren’t cognitively impaired.

At 5 weeks, the researchers gave the three groups of rats a memory test in a maze. As expected, the cognitively impaired rats had more trouble than the unimpaired control rats. But after a few days, the cognitively impaired rats who had done strength training matched—and in some cases exceeded—the ability of the control rats. The sedentary rats lagged far behind.

To the researchers, this indicated that weight training was able to reverse the impairment caused by neuroinflammation, even though the inflammation in their brains was still present.

Examination of the rats’ brains showed increased activity in downstream IGF-1 [Insulin-Like Growth Factor 1], indicating that new neurons were generated.

IGF-1 is one of the most potent natural activators of the AKT signaling pathway, a stimulator of cell growth.

The researchers also found molecular signs of increased neuroplasticity, suggesting that the weight-trained rats had recovered some brain function despite their cognitive impairment.

Simply put, progressive weight training caused the rats to repair or create neurons (brain cells).

“This model offers a potential therapy that may prevent or delay the onset of mild cognitive impairment in neurodegenerative diseases that warrants further investigation,” the authors concluded.

As the study authors wrote, more research needs to be done. In the meantime, they added, weight training to stave off age-related cognitive impairment and memory loss is certainly worth trying.

“This is an option for the elderly,” Frank W. Booth, PhD, Professor, Department of Biomedical Sciences, University of Missouri, Columbia, MO, said to the Columbia Daily Tribune. Dr. Booth was one of the authors and he funded the study out of his own pocket. “You see old individuals just sitting around. If they start using their muscles, it will be helpful to society.”

In an interview with The New York Times, lead author and doctoral candidate Taylor Kelty said: “I think it’s safe to say that people should look into doing some resistance training. It’s good for you for all kinds of other reasons, and it appears to be neuroprotective. And who doesn’t want a healthy brain?”

(The Abstract alone was online, so I wasn’t able to examine the entire study. The quotes and much of the information presented here comes from an article by John Murphy in MDLinx.)

My Take

Some give this study short shrift, pointing out that what works for rats doesn’t necessarily work for humans. They discount that people could not be subjected to cognitive impairment for research purposes. These rats took the insult and lifted their way back to normalcy.

I’m encouraged by the study. It gives me confidence that my lifetime of lifting, combined with whole body aerobics and a balanced diet of whole foods will allow me to hold off senility for a long time. My grandmother had her wits about her until her death just short of 100. She never touched a weight - people in her time didn't exercise - but some centenarians now do.

The Sunday, June 21, 2020, Parade magazine includes a photo of Ruth Kundsin, 103, doing leg presses. You can listen to her talking with her trainer and lifting on YouTube:


Thanks to the gym rats - and Ruth Kundsin - for helping to confirm that progressive resistance exercise is an important part of healthy aging.


Rats can’t track progress, but we can. Building success on success can keep us going for a lifetime.

Photo by Greg Kuehn

July 1, 2020

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