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NEUROSCIENCE

Movement for the brain

Exercise in pregnancy and childhood has long-lasting effects on intellectual performance

Exercício_Scan1330NegreirosIf you want to improve your children’s chances of being high achievers both intellectually and professionally, the worst thing you can do is radically cut their exercise time to make room for more hours of sedentary study. Not only that, mothers should ideally also break a sweat during pregnancy, according to neuroscientist Sérgio Gomes da Silva, researcher at the Albert Einstein Israelite Institute for Education and Research, in the city of São Paulo.

Gomes da Silva uses rats as research models to understand the effects of physical activity on brain development. In his most recent findings, published in PLOS One in January 2016, the researcher and his collaborators showed that when female rats exercised on a treadmill during gestation, their pups were born with a “pumped up” hippocampus, a brain region involved mainly in functions related to memory, learning and emotions. The hippocampi of these offspring have more cells and more brain-derived neurotrophic factor (BDNF), a protein that regulates brain cell proliferation, development and differentiation processes. There is a detectable difference not only at the cellular level, but also in behavior, as shown by tests that measure how fast an animal learns to recognize an experimental territory. In an arena where rat pups needed to memorize reference points, the offspring of mothers who had exercised learned faster. “Their intelligence scores are higher,” says the researcher.

During previous studies performed in collaboration with Ricardo Mario Arida from the Federal University of São Paulo (Unifesp), in whose laboratory Gomes da Silva completed his doctorate and postdoctorate, da Silva had already shown that physical exercise during adolescence made rats smarter. In spatial memory tests using tiny swimming pools, in which the animals had to learn to find a submerged platform where they could stand, rodents that had followed an exercise program performed better, according to an article published in 2012 in the journal Hippocampus. BDNF also seems to be responsible in this case, as the protein is more abundant in trained rats and is believed to help form hippocampal cell fibers that improve the performance of this region of the brain. In addition, according to Gomes da Silva, these rats also have a greater number of interneurons, the cells that enable animals to tune out irrelevant environmental information and concentrate on a given task. An analogous human situation would be the ability to study without paying attention to a nearby TV or to the pressure of the chair against one’s back.

The most important finding was that the effect lingers into adulthood, in the case of rats. “When people stop exercising, they quickly lose muscle mass,” notes Gomes da Silva. “We showed that the brain works differently: if it was formed in an enriched manner, the developmental alterations produced during childhood will remain throughout life.” This makes sense, since brains are not fully developed at birth. A human brain specifically, which in newborns weighs around 300 grams, will not reach its final size of 1.5 kilogram until one’s late teens.

The neuroscientist also performed induced epilepsy tests and found evidence that exercise in childhood has long-lasting benefits in this regard as well. In an article published in 2011 in the International Journal of Developmental Neuroscience, he showed that a group of 14 rats that followed a treadmill training program during childhood and adolescence had much milder convulsions after being injected with an inducing substance, when compared to 14 other subjects with lazier habits. This finding supports the neural reserve hypothesis, which postulates that a brain under these enriched conditions will produce a higher number of cells, generating structures that are more complex and versatile. If some neurons fail, others are available to pick up the slack and correct the error.

Exercício_Scan1331NegreirosFrom rats to humans
The greatest achievement of Gomes da Silva’s work came in 2013, when his article was cited by a Swedish study led by Jenny Nyberg at the University of Gothenburg, which showed that exercise during adolescence provides life-long protection against epilepsy. The subjects in this case were a large population of humans. “My study on 28 rats was supported by a group of over a million people,” says the Brazilian researcher. The Swedish group collected military recruitment data from the period between 1968 and 2015 and then looked at the medical records of those people – a history of up to 40 years, in the case of the oldest patients. The results showed that low physical fitness at age 18 was associated with increased epilepsy risk in adulthood, and also that being in good shape offered long-lasting protection against cardiovascular diseases, depression and diabetes, not to mention premature death.

According to Nyberg, these and other results provide compelling evidence that exercise helps form a more plastic and robust brain, both in humans and other animals. She believes that this complementarity between studies performed on people and laboratory animals has been productive. “Physiological mechanisms and processes are much harder to study in humans,” she says. “With animals, we can look at the brain and see what actually happens, and understand why physical activity is positive for brain health.” Her group also detected a correlation between low physical and cognitive performance at 18 and the occurrence of premature dementia, according to an article published in Brain in 2014.

In Brazil, the work of physical education specialist Marlos Domingues, from the Federal University of Pelotas in the state of Rio Grande do Sul, revealed further evidence of the similarity between results obtained from rodents and what happens with people. Domingues collected long-term studies conducted in the city of Pelotas to assess the effects of physical activity during pregnancy on fetal neurological development.

In a monitoring project that involved almost 4,000 babies born in 2004, children of active mothers performed better on cognitive tests throughout their first year of life, with a stronger difference observed among boys. The effect was gradually lost in subsequent years, according to the article published in PLOS One in 2014. “At that age, other environmental factors start coming into play,” Domingues explains. Human cognitive development can be affected by a vast range of environmental factors, including social interactions and access to reading. In light of this, the researcher believes that a mother’s education has an influence on the IQ of her children and is also associated with physical activity, in his experience. This difficulty in discerning the relevant factors in humans emphasizes the importance of studies on rodents. “There is no difference in schooling among rats,” he jokes.

Domingues does not discard the possibility of long-term effects, however. “Thirty years from now, there may be a difference,” he speculates, which would be in line with Gomes da Silva’s recent findings for adult rats. Although the researchers from Pelotas have been monitoring the city’s population since the 1980s, they did not start asking mothers about exercise in pregnancy until 2004. Even so, the assessment was quite superficial, based only on a questionnaire administered after they had already given birth. “In 2015, we collected more accurate information, with measurements taken using accelerometers during pregnancy,” says Domingues. It will take a few years for the researchers to know whether this will reveal stronger signs of the benefits of exercise during that stage.

Trained rats (right) make more neural connections in the dentate gyrus, a part of the hippocampus associated with certain memories, such as environmental reconnaissance

Sérgio Gomes da Silva / Albert Einstein Trained rats (right) make more neural connections in the dentate gyrus, a part of the hippocampus associated with certain memories, such as environmental reconnaissanceSérgio Gomes da Silva / Albert Einstein

Gender distinction
The difference between boys and girls suggested by the research conducted in Pelotas was also detected in the study led by Irene Esteban-Cornejo from the University of Madrid, in Spain, which analyzed almost 2,000 children ages six to 18. The results, published in 2016 in The Journal of Maternal-Fetal & Neonatal Medicine, show that physically active women have children who do better in school according to several performance indexes, including language and math – even if the children themselves do not maintain the same level of activity as their mothers. The effect was stronger when exercise was already a habit before pregnancy and was maintained throughout gestation; running to the gym after getting a positive test is not enough. Apparently, the same effect is not seen in girls. No one knows exactly why yet, but the most widely accepted explanation seems to be that their brains are naturally more “pumped up” in terms of cells and connections, giving environmental benefits little room to contribute.

Sérgio Gomes da Silva calls attention to the importance of the knowledge that these studies are bringing to light, when planning the school activities of children and teens. “By law, Brazilian schools are required to offer two hours of physical activity a week,” he says, “but the World Health Organization recommends an hour every day for teenagers, divided into two sessions if necessary.” If they want to see effective learning and future professional success, schools and families will likely need to rebalance exercise and reading time for kids.

Projects
1.
Exercise and prenatal brain development: a study in rat pups born from mothers trained during pregnancy (nº 2010/11353-3); Grant Mechanism Scholarship in Brazil – Regular – Postdoctoral; Principal Investigator Ricardo Mario Arida (EPM-Unifesp); Recipient Sérgio Gomes da Silva; Investment R$226,782.32
2. Brain plasticity induced by physical exercise (nº 2009/06953-4); Grant Mechanism Thematic Project; Principal investigator Ricardo Mario Arida (EPM-Unifesp); Investment R$324,748.94

Scientific articles
GOMES DA SILVA, S. et al. Maternal exercise during pregnancy increases BDNF levels and cell numbers in the hippocampal formation but not in the cerebral cortex of adult rat offspring. PLoS One. V. 11, No. 1. Jan. 15, 2016.
GOMES DA SILVA, S. et al. Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats. Hippocampus. V. 22, No. 2, pp. 347-58. Feb. 2012.
GOMES DA SILVA, S. et al. Early physical exercise and seizure susceptibility later in life. International Journal of Developmental Neuroscience. V. 29, No. 8, pp. 861-65. Dec. 2011.
NYBERG, J. et al. Cardiovascular fitness and later risk of epilepsy – A Swedish population-based cohort study. Neurology. V. 81, No. 12, pp. 1051-7. Sep. 17, 2013.
DOMINGUES, M. R. et al. Physical activity during pregnancy and offspring neurodevelopment and IQ in the first 4 years of life. PLOS One. V. 9, No. 10. Oct. 28, 2014.
ESTEBAN-CORNEJO, I. et al. Maternal physical activity before and during the prenatal period and the offspring’s academic performance in youth. The Journal of Maternal-Fetal & Neonatal Medicine. V. 29, No. 9, pp. 1414-20. May 2016.

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