Chronicles

The development of the brain is a complex process that involves a sequence of events at molecular and cellular levels that are regulated both time and space-wise in a coordinated way.

In short, the development of the brain starts with the formation of the cells that will compose it, those being immature neurons and glial cells. After the formation of these cells, the following event is the process of migration, that will decide the final position of each neuron on the brain, determining the brain’s cito-arquitecture over which synapses are established. Synapses are structures specialized in the conduction of information between neurons, and its formation is known as the process of synaptogenesis. These synaptic networks represent the biological and physiological basis that allows the brain to perform all its functions, from the more basic ones to the most complex cognitive functions.

All these processes do not only take place during the embryogenesis, that is, in a prenatal phase, but also during infancy and adolescence until reaching adulthood, at which point the brain still preserves certain plasticity. All these processes, obviously depend on the genetic information of an individual. Several brain malformations associated to defects on genes that code for proteins involved in brain development have been reported. However, the development of the brain is also dependent on and susceptible to environmental or external factors to which we are exposed either at prenatal or postnatal stages. There is evidence, both in laboratory animals and humans, that indicates that physical activity is one of these factors, capable of positively influencing brain development. This positive contribution occurs not only in a postnatal phase during infancy and adolescence through the physical activity performed by the individual himself, but also during the prenatal period. In lab animal models, it was observed that the cognitive performance – namely learning and memory – of the offspring of progenitor rats that performed physical activity during pregnancy was improved compared to those that did not. In the same way, human research has demonstrated that children of mothers that practiced exercise during pregnancy perform better in tests that evaluate different cognitive functions (general intelligence, oral expression etc.) and have a higher academic success.

In addition to the benefits observed in the capacities of the brain, there is evidence that exercise practice during pregnancy has also neuroprotective effects. For instance, a study with laboratory animals showed that maternal exercise during pregnancy reduces the capacity to induce diseases such as Alzheimer’s Disease in the descendants, even in the absence of postnatal exercise practice. These results suggest that maternal prenatal physical activity alone is able to lower the risk of developing neurogenerative diseases such as Alzheimer’s Disease.

During infancy and adolescence, a critical period for the maturation of the brain and for the fine-tuning of the synaptic networks, a phenomenon that predominantly depends on external stimuli, evidence is even more robust regarding the positive effect of exercise practice on brain development. A clear positive correlation between physical activity and cognitive performance, including learning, processing speed, concentration, reaction time and rigor in academic testing has been observed. This in turn, improves not just the executive functions of the brain, but also creativity, effects that carry into adulthood and to which a lower probability of cognitive decline during aging is associated.

These evidences are corroborated by similar results obtained with animal models. In summary, several studies with rodents testing different exercise training programs revealed a general improvement in memory and learning with long-lasting effects, and in general a sustained healthier brain which renders it less susceptible to the development of diseases. Furthermore, other evidence suggest that postnatal physical activity makes the brain more resistant to the future development of diseases and has beneficial effects for brain activity in neurodevelopmental diseases such as Rett syndrome, X fragile syndrome or schizophrenia.

From a neurobiological standpoint, several factors could be at the basis of this positive effect of physical activity on the development of the brain. It has been reported in rodents, that different types of physical exercise during pregnancy induce an increase in the proliferation and differentiation of neurons in the offspring, namely in the hippocampus, an essential brain region for learning and memory processes. These effects are likely associated to modifications in the expression of some proteins, predominantly through epigenetic regulation, namely trophic factors such as the protein BDNF that regulates the proliferation and differentiation of neurons, dendritic arborization, synaptogenesis and synaptic plasticity, the last one being the cellular basis for learning and memory. In fact, a study demonstrated that an improvement in spatial memory observed in offspring of rats that performed physical activity during pregnancy was inhibited with the blockage of BDNF’s action. A reduction of stress associated to physical activity could also be an important factor, since it was demonstrated in animal models that maternal stress during gestation interferes with the migration of neurons during embryogenesis, a phenomenon that could be related to an increase in glucocorticoids.

As observed in the case of prenatal exercise, postnatal exercise has also been associated to an increase in the levels of BDNF in juvenile rodents. An increase in the cognitive capacity due to physical exercise was also prevented by blocking the action of BDNF, indicating that an improvement in the cognitive capacity depends on the levels of this protein, which is in turn, probably associated to an increase in neurogenesis (higher number of cells) as well as in synaptic network complexity induced by postnatal exercise.

In conclusion, brain development is a complex process that even if programmed by the genetic make-up of an individual, depends and it is strongly influenced by external stimuli. There is clear evidence supported by experimental data that show that exercise practice during pregnancy, infancy and adolescence improve the cognitive capacity and make the brain healthier and more resistant to aging and disease. This evidence also demonstrate that physical activity early in life, that is during development, has robust and long-lasting effects on the adult brain, with an even bigger impact than physical activity performed in adulthood. It is nonetheless fundamental to continue these studies to better understand the neurobiological and neurochemical basis of the beneficial effects of physical exercise for the development of the brain as well as to characterize the impact of different exercise training programs regarding type, intensity, frequency and duration. We are only at the beginning of the marathon. We have still lots of kilometers to run before reaching the finish line.

Author:  Ricardo J. Rodrigues and Joana M. Marques are Researchers at the Center for Neuroscience and Cell Biology (CNC), University of Coimbra (UC).

The project: This chronicle results from the collaboration between the Center for Neuroscience and Cell Biology (CNC) of the University of Coimbra, the European Advanced Training Network FOIE GRAS (http://www.projectfoiegras.eu), the Erasmus+ Program and the Academic Sports Federation University (FADU) in the scope of the European University Games Coimbra 2018.

Coordination: Anabela Marisa Azul, João Ramalho-Santos, Mireia Alemany i Pagès, Paulo Oliveira and Sara Varela Amaral

Illustration: Rui Tavares