How Exercise Promotes Adaptive Structural and Functional Changes to Your Brain

The neuroscience of fitness, a fascinating intersection of physical activity and brain health, is a rapidly developing area of research. This field explores the profound effects of regular exercise on our brain and nervous system, revealing significant implications for our overall health and quality of life.

One of the major benefits of exercise is the creation of new brain cells, which is known as neurogenesis. Within the hippocampus, a brain structure crucial to learning and memory, there are cells known as neural progenitors that can give rise to new brain cells.

Recently, there has been debate about whether humans make new neurons throughout life.

Research in rodents have demonstrated that neurogenesis in adulthood helps keep certain cognitive skills sharp, including the ability to learn about the physical environment and remember how to navigate it. In fact, some studies have linked regular exercise to neurogenesis.

Newborn hippocampal neurons that survive in their brains have doubled in animals that exercise. These animals also showed enhanced memories and markers of neurogenesis⁽¹⁾.

Brain plasticity, neurogenesis, and exercise 

The capacity of the brain to adapt to ever-changing conditions (known as brain plasticity) depends on the ability of neurons (i.e., brain cells) to modify the strength and composition of their connections in response to both external and internal stimuli. The long-term potentiation in synaptic efficacy (the strength of communication between neurons) forms the physiologic base for learning and memory. An important way for regulating neuronal function is the activity-dependent synapse-to-nucleus signaling, that can arise both in the post-synaptic and in the presynaptic element ⁽²⁾.

Through the tight regulation of synapse to nucleus signaling, this activation of the synapse causes the specific gene expression programs necessary for learning and memory. Evidence demonstrates that impaired function of these signaling proteins causes intellectual disability, psychiatric disorders, or neurodegeneration⁽³⁾.

Essentially, we can infer that increasing their function, as a response to physical activity, could also enhance brain function and plasticity.

Traditionally, it was accepted that new neurons could not be generated in the adult to replace dying cells, and this limitation was considered the chief cause of neurodegeneration as well as cognitive decline in the elderly population. However, since the 1960s, evidence indicates that new neurons could be generated in the hippocampus and the lateral ventricles⁽⁴⁾.

Particularly, neurons born in the hippocampus differentiated and integrated into the local network of the hippocampus. These are very important findings since the hippocampus is central for the formation of certain types of memory (e.g. episodic or spatial memory)⁽⁵⁾.

Additionally, hippocampus-dependent learning is one of the major regulators of hippocampal neurogenesis⁽⁶⁾ which essentially means that when an individual lives within an environment that stimulates learning, this in affect enhances the survival of neurons⁽⁵⁾.

Mechanisms of action

Exercise triggers the release of a protein called brain-derived neurotrophic factor (BDNF), which nurtures existing neurons and encourages the growth and development of new neurons and synapses.

Evidence shows that cardiovascular exercise like running and swimming are particularly beneficial. This type of activity as a synergistic effect of stimulating neurogenesis and increasing the size of the anterior hippocampus, which leads to an improvement in spatial memory. In addition, this type of exercise is linked to the preservation of white and gray matter in the frontal, temporal, and parietal areas of the brain, which characteristically shrink with age and are essential for cognitive function.

Another crucial and positive effect of exercise is that it releases neurotransmitters, including serotonin, dopamine, and norepinephrine.

These chemicals play an essential role in mood regulation, mental alertness, and focus, potentially explaining why physical activity is often associated with reduced symptoms of depression and anxiety. 

Recent evidence shows that BDNF is necessary for dopamine release because BDNF catalyzes increased dopamine signaling. This research demonstrated that exercise showed an increase in dopamine that remained elevated up to a week after the exercise period ended⁽⁷⁾.

Figure: This figure demonstrates an increase in dopamine in the exercise model. Adapted from Bastioli et al.⁽⁷⁾. 

We all know the importance of sleep for enhancing all aspects of our life. Regular exercise improves the quality of our sleep, which is a crucial factor in brain health.

Enhancing the quality of sleep promotes enhanced memory consolidation and more efficient toxin removal from the brain.

A very important and recent finding is that vigorous exercise was able to modulate various sleep parameters associated with improved sleep, without the participants subjectively noticing this improvement. This study concluded that although vigorous exercise does not lead to a subjective improvement in sleep quality, sleep function is improved based on objective measures such as electroencephalogram (EEG) parameters⁽⁸⁾.

Exercise promotes brain plasticity, the brain’s ability to adapt and form new neural connections throughout life.

This is especially important for recovery from a brain injury and counteracting the cognitive decline associated with aging. Recent work utilized a cutting-edge analytical technology (i.e., high-density oligonucleotide microarray analysis) and demonstrated that, in addition to enhancing levels of BDNF, exercise mobilized gene expression profiles that would be predicted to benefit brain plasticity processes.

By inducing BDNF and other molecules, exercise enhances neuronal structure and facilitates synaptic transmission, thus, priming activated cells for encoding⁽⁹⁾.  

Figure: Effects of exercise on hippocampal brain-derived neurotrophic factor (BDNF) mRNA and protein levels. Adapted from Cotman and Berchtold⁽⁹⁾.

Additionally, exercise can enhance various cognitive functions, including attention, working memory, executive function, and cognitive flexibility. The prefrontal cortex, a brain area responsible for these functions, appears to respond positively to physical exercise, likely due to the increased blood flow, which delivers more oxygen and nutrients to the brain.

Summary

Despite these promising findings, there is still much to explore in the neuroscience of fitness. Questions remain about how different forms of exercise (such as aerobic vs resistance training) impact the brain and how factors like age, genetics, and initial fitness level may influence these effects.

However, the current evidence strongly supports that regular physical activity has significant benefits for brain health and cognitive function, emphasizing the value of integrating regular exercise into our daily lives for physical and mental health benefits.

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References:
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2.    Ch'ng, T.H., et al., Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus. Cell, 2012. 150(1): p. 207-21.
3.    Parra-Damas, A. and C.A. Saura, Synapse-to-Nucleus Signaling in Neurodegenerative and Neuropsychiatric Disorders. Biol Psychiatry, 2019. 86(2): p. 87-96.
4.    Altman, J. and G.D. Das, Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol, 1965. 124(3): p. 319-35.
5.    Deng, W., J.B. Aimone, and F.H. Gage, New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci, 2010. 11(5): p. 339-50.
6.    Gould, E., et al., Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci, 1999. 2(3): p. 260-5.
7.    Bastioli, G., et al., Voluntary Exercise Boosts Striatal Dopamine Release: Evidence for the Necessary and Sufficient Role of BDNF. J Neurosci, 2022. 42(23): p. 4725-4736.
8.    Park, I., et al., Exercise improves the quality of slow-wave sleep by increasing slow-wave stability. Sci Rep, 2021. 11(1): p. 4410.
9.    Cotman, C.W. and N.C. Berchtold, Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci, 2002. 25(6): p. 295-301.