Mouse study shows offspring of active fathers are better at learning and remembering

By Valerie Nikolas
Medill Reports

Men, if you want smarter kids, it may be time to hit the gym.

When it comes to baby-bearing, women often get the brunt of the responsibility, especially before a child is born. But new evidence shows that a dad’s morning run or lifting session may be responsible for more of his offspring’s cognitive traits than previously thought.

Researchers at the Cajal Institute, a neuroscience research center in Madrid, found in a study with mice that offspring of active fathers learn and recall information better than the offspring of sedentary dads. The study, published last month in the Proceedings of the National Academy of Sciences (PNAS), cites “paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.”

“Exercise is not only good for you—the person who is doing the exercise—but also for your sons or daughters,” said neuroscientist José Luis Trejo, the study’s lead researcher.

Trejo and his team found that mice with active fathers not only had more neurons present in their brains, they also had more activity occurring within these cells, and they performed better on cognitive tests.

Researchers exposed one group of male mice to an exercise regimen of running on a wheel every day for six weeks, while the other group stayed sedentary. Both groups of fathers bred, and their offspring were subjected to behavioral tests and brain analysis.

The active fathers’ offspring performed significantly better at distinguishing between similar objects in spatial recognition tests. Also, they had more neurons and higher levels of mitochondrial activity in the hippocampus, the region of the brain responsible for learning and memory.

Testing showed the benefits in offspring were not due to changes in their sequences of DNA code, but rather changes in the RNA, the molecules responsible for expressing those sequences.

“The genetic changes are doing all the things,” Trejo said. “It’s epigenetics.”

Trejo’s team performed RNA sequencing on the mice’s genetic information and found differences in microRNA, or miRNA, the small molecule bits that control gene expression by occupying short strands of DNA. The presence of miRNA on a bit of DNA code determines whether that piece of the code expresses or doesn’t express.

Having a dad who exercised does not change the sequences that compose a mouse’s DNA, but it does change the genes on that genetic code by allowing more favorable states of brain function to occur.

For example, explained Trejo, “some genes in the nucleus of these mice’s sperm are modifying the mitochondria the offspring inherited through the mother,” thus causing more active mitochondria.

Intergenerational effects of parental experiences have become a global research focus in recent years. The Cajal Institute study builds on an Ohio State University study from 2018 that found offspring of active father mice have better metabolisms. It also mirrors another study published last year, by Benito and Fischer, et. al., that linked enriching father mice’s environments to improved cognition in their offspring.

“We are the first, as far as I know, to report clear, positive effects in behavior [from] exercising fathers,” Trejo said.

Because many genetic similarities exist between mouse and human brains, and because performing mouse studies is much easier (and more ethical) than human studies, researchers often extrapolate mouse study findings to humans. Although mouse studies do shed insight on the brain, limitations still exist.

“Science is still using mouse models to study brain structure,” said Javier DeFelipe, a research professor at the Cajal Institute. “If you’re trying to understand the human brain, ideally you need to study the human brain. But, in some studies, when you manipulate the mice you can assume the human [results] will be the same.”

PNAS will highlight the Cajal Institute study as a special feature in the May 14 edition of its print journal.

After working on this study for more than four years, Trejo’s team is expanding on their findings. They’d like to determine if the same results apply to females. The team expects they will.  And they want to find out if these cognitive benefits extend to grandchildren.

In the meantime, Trejo said, “If you’re thinking about having kids, exercise is something good you can do for them because they will have a higher number of neurons, with healthier mitochondria, and this all leads to being smarter.”