This is Your Brain on Exercise

Exercise is well-known for its cardiovascular and musculoskeletal benefits, and even its impacts on stress. But its effects on the brain are equally profound, if not more so. Regular physical exercise produces extraordinary benefits on the brain from a neuroscientific perspective. One of the most significant effects is the stimulation of neurogenesis, particularly in the hippocampus, a brain region crucial for learning and memory. Exercise also increases the production of brain-derived neurotrophic factor (BDNF), a protein that supports the survival and growth of neurons and promotes the formation of new synapses, thereby enhancing memory capacity and cognitive function. Aerobic activities such as running and swimming have been shown to increase the size of the hippocampus, preserve gray and white matter, and improve spatial memory, all of which are essential for maintaining cognitive health throughout life.

Beyond structural changes, exercise induces functional improvements in brain activity and connectivity. Regular physical activity enhances neuroplasticity-the brain’s ability to adapt and form new neural connections-which is vital for recovery from injury, learning new skills, and counteracting age-related cognitive decline. These neuroplastic changes are associated with improved executive functions, such as attentional control, working memory, cognitive flexibility, and decision-making. Studies have demonstrated that individuals who consistently engage in aerobic and resistance exercise exhibit better performance on neuropsychological tests measuring these cognitive domains compared to sedentary individuals.

Physical activity (PA) also exerts powerful effects on mood and stress regulation through multiple neurochemical pathways. PA increases levels of neurotransmitters like serotonin, dopamine, and norepinephrine, which are integral to mood regulation, mental alertness, and focus. This neurochemical boost helps reduce symptoms of depression and anxiety, while also improving sleep quality, which in turn supports memory consolidation and the removal of metabolic waste from the brain through supporting the glymphatic system. The glymphatic system is a specialized waste clearance pathway in the brain that facilitates the removal of metabolic byproducts, excess fluid, and neurotoxic proteins such as beta-amyloid from the central nervous system. This system operates mainly during sleep, when cerebrospinal fluid (CSF) flows along perivascular spaces, mixes with interstitial fluid, and is then cleared through perivenous routes, ultimately draining toward the cervical lymphatic system. Efficient glymphatic function is essential for maintaining brain health and preventing the buildup of substances associated with neurodegenerative diseases like Alzheimer’s. PA has a positive impact on the glymphatic system by promoting cardiovascular health, increasing arterial pulsatility, and supporting healthy sleep patterns-all factors that enhance glymphatic clearance. Exercise-induced improvements in vascular function help drive the convective movement of CSF and interstitial fluid, facilitating more effective waste removal from brain tissue. Additionally, regular physical activity is linked to better sleep quality, which is crucial because glymphatic activity is most robust during deep sleep, further supporting efficient brain detoxification and potentially reducing the risk of neurodegenerative disorders. Collectively, these neuroscientific findings underscore the importance of regular exercise not only for physical health but also for optimizing brain function and mental well-being.

Neuroscientific research increasingly reveals that exercise promotes cognitive function, emotional regulation, neuroprotection, and neuroplasticity through complex hormonal and molecular mechanisms. This article reviews the major neurochemicals influenced by exercise—including brain-derived neurotrophic factor (BDNF), dopamine, serotonin, endorphins, norepinephrine, and cortisol—and explains how these substances mediate the relationship between movement and mental well-being. For centuries, movement has been linked with mental clarity and emotional stability. Only recently, however, have neuroscientists begun to uncover the specific pathways by which exercise influences brain structure and function. With the rise of neuroimaging and molecular biology tools, a clearer picture has emerged: exercise is one of the most effective non-pharmaceutical interventions for improving brain health across the lifespan. Let's take a look at each one individually to see the specific impacts they have on our brains.

Brain-Derived Neurotrophic Factor (BDNF)

BDNF is a protein that supports the survival, growth, and differentiation of neurons. It plays a critical role in neuroplasticity, the brain’s ability to adapt by forming new neural connections. Brain-derived neurotrophic factor (BDNF) is a neurotrophin-a type of protein crucial for the development, maintenance, and plasticity of neurons in the central and peripheral nervous systems. BDNF is especially abundant in brain regions vital for learning, memory, and higher cognitive functions, such as the hippocampus and cortex. It supports the survival of existing neurons, encourages the growth and differentiation of new neurons and synapses, and plays a central role in synaptic plasticity, which underlies learning and memory formation. BDNF is initially synthesized as a precursor, proBDNF, which can have effects distinct from its mature form; while mature BDNF (mBDNF) binds to TrkB receptors to promote neuronal survival and synaptic strengthening, proBDNF may bind to p75NTR receptors and can induce synaptic weakening or even apoptosis. Importantly, BDNF levels can be significantly increased by physical exercise, contributing to enhanced neurogenesis and cognitive function. (Cotman et al., 2007; Szuhany et al., 2015)

• Mechanism: BDNF enhances long-term potentiation (LTP), a cellular process underlying learning, and protects against neurodegeneration.

Dopamine

Dopamine is a neurotransmitter that plays a central role in the brain’s reward, motivation, movement, and cognitive functions. It is produced in specific brain regions, including the ventral tegmental area and substantia nigra, and acts by transmitting signals across several major pathways such as the mesolimbic, mesocortical, and nigrostriatal systems. Dopamine is often referred to as the “pleasure molecule” because it is heavily involved in the brain’s reward circuitry, reinforcing behaviors that produce feelings of enjoyment and motivating individuals to repeat those behaviors. Beyond its role in pleasure and reinforcement, dopamine is essential for regulating voluntary movement, executive function, attention, learning, and mood. Dysfunction in dopamine signaling can lead to a range of neurological and psychiatric disorders, such as Parkinson’s disease, which is characterized by motor deficits due to degeneration of dopaminergic neurons in the nigrostriatal pathway, and various mood and addiction disorders linked to dysregulation in the reward pathways.Exercise and Dopamine: Regular physical activity increases dopamine receptor availability and dopamine release, particularly in the striatum and prefrontal cortex (Robertson et al., 2016). This contributes to increased motivation and reduced symptoms of depression and ADHD.

• Mechanism: Exercise enhances dopaminergic neuron survival and reduces neuroinflammation, especially relevant in disorders like Parkinson’s disease.

Serotonin

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a neurotransmitter with wide-ranging effects on both the central nervous system and the body as a whole. In the brain, serotonin plays a key role in regulating mood, sleep, appetite, memory, and learning, often earning it the reputation of being a natural mood stabilizer. Approximately 90% of the body’s serotonin is produced in the gastrointestinal tract, where it helps control bowel movements and digestive function, while the remaining portion is synthesized in the brain, where it influences emotional well-being, cognition, and sleep cycles. Serotonin is also involved in other physiological processes such as blood clotting, wound healing, and sexual function, and it acts as both a vasoconstrictor and vasodilator depending on concentration and context. Imbalances in serotonin levels are linked to mood disorders such as depression and anxiety, which is why many antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), target serotonin pathways to help restore emotional balance.Exercise and Serotonin: Acute and chronic exercise increase serotonin synthesis and receptor sensitivity in the raphe nuclei and forebrain (Meeusen & De Meirleir, 1995).

• Mechanism: Tryptophan availability in the brain increases during exercise, promoting serotonin synthesis and improving mood.

Endorphins

During exercise, the brain releases endorphins, a group of endogenous opioid peptides that play a crucial role in modulating pain, stress, and mood. Beta-endorphins, in particular, are released in greater quantities during both acute bouts of exercise and regular training, especially at moderate to high intensities. These endorphins bind to opioid receptors in the brain, reducing the perception of pain and producing feelings of pleasure and euphoria, often referred to as the “runner’s high”. The release of endorphins not only helps individuals manage the physical discomfort associated with intense physical activity but also contributes to improved mood and stress relief, supporting motivation for regular exercise. While the exact relationship between peripheral endorphin levels and immediate mood changes is still being studied, evidence suggests that endorphin release is a key mechanism underlying the psychological and physiological benefits of exercise, including enhanced well-being and resilience to stress.Exercise and Endorphins: Exercise induces a surge of β-endorphins, particularly during high-intensity workouts. This is associated with the well-known “runner’s high” (Boecker et al., 2008).

• Mechanism: Endorphins bind to opioid receptors in the brain, reducing pain perception and elevating mood.

Norepinephrine (Noradrenaline)

Norepinephrine is also known as noradrenaline, and is both a neurotransmitter and hormone that plays a vital role in the brain and body’s response to stress, arousal, and attention. In the central nervous system, norepinephrine is primarily produced in the locus coeruleus and is critical for promoting wakefulness, alertness, and vigilance, as well as enhancing the formation and retrieval of memories and focusing attention. It is a key component of the “fight or flight” response, rapidly mobilizing the body and brain to respond to perceived threats by increasing heart rate, blood pressure, and blood glucose levels, while also diverting blood flow to muscles and away from less immediately necessary functions like digestion. Beyond its role in acute stress, norepinephrine helps regulate biorhythms such as the sleep-wake cycle, supports mood stability, and influences cognitive functions like working memory and behavioral flexibility through its action on various adrenergic receptors in the brain.Exercise and Norepinephrine: Physical activity increases norepinephrine levels in the locus coeruleus and the prefrontal cortex, improving attention and executive functioning (McMorris et al., 2008).

• Mechanism: It enhances neural responsiveness and facilitates task-switching and decision-making.

Cortisol

Cortisol is a steroid hormone (glucocorticoid) produced by the adrenal glands and is widely known as the body’s primary “stress hormone.” Its release is regulated by the hypothalamic-pituitary-adrenal (HPA) axis, particularly in response to stress, but it also follows a daily rhythm-peaking in the early morning and declining at night. Cortisol plays a vital role in the “fight-or-flight” response, helping the body respond to danger by increasing blood glucose for quick energy, supporting alertness, and modulating heart rate and blood pressure. Beyond stress, cortisol is essential for regulating metabolism, reducing inflammation, and supporting immune function. While short-term increases in cortisol can be beneficial, chronically high or low levels can lead to health problems, such as weakened immunity, high blood pressure, or metabolic disturbances. Thus, maintaining balanced cortisol levels is crucial for overall health and well-being. Its relationship with exercise is complex. Moderate exercise reduces baseline cortisol levels over time, improving stress resilience. However, intense or prolonged exercise can temporarily elevate cortisol (Hill et al., 2008).

• Mechanism: Adaptation to exercise stress improves hypothalamic-pituitary-adrenal (HPA) axis regulation, reducing chronic stress effects on the brain.

Neurogenesis and Structural Brain Changes

Physical activity also enhances white matter integrity, increases cortical thickness, and slows age-related brain atrophy (Erickson et al., 2011). Exercise induces significant neurogenesis and structural changes in the brain, particularly in the hippocampus, a region critical for learning and memory (van Praag et al., 1999). Regular physical activity, especially aerobic exercise, stimulates the creation of new neurons (a process known as neurogenesis) primarily in the hippocampus, which enhances memory, learning, and cognitive function. Structural changes due to exercise include increased hippocampal volume, preservation of gray and white matter, and improved connectivity within neural networks, all of which contribute to better executive function, spatial memory, and overall cognitive performance. These effects are most pronounced with consistent, long-term exercise, which accelerates the development and integration of new neurons, leading to more complex and efficient neural networks compared to a sedentary lifestyle.

The impact of physical activity on the brain is both broad and powerful. From molecular messengers like BDNF and serotonin to large-scale structural changes in the brain, physical activity serves as a potent modulator of mental and cognitive health. Incorporating regular exercise—especially aerobic movement and activities like dance—into daily life should be a foundational recommendation in both medical and mental health care.

References

1. Boecker, H., Sprenger, T., Spilker, M. E., et al. (2008). The runner’s high: Opioidergic mechanisms in the human brain. Cerebral Cortex, 18(11), 2523–2531.

2. Cotman, C. W., Berchtold, N. C., & Christie, L. A. (2007). Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in Neurosciences, 30(9), 464–472.

3. Erickson, K. I., Voss, M. W., Prakash, R. S., et al. (2011). Exercise training increases size of hippocampus and improves memory. PNAS, 108(7), 3017–3022.

4. Hill, E. E., Zack, E., Battaglini, C., et al. (2008). Exercise and circulating cortisol levels: the intensity threshold effect. Journal of Endocrinological Investigation, 31(7), 587–591.

5. McMorris, T., Collard, K., Corbett, J., et al. (2008). A test of the catecholamines hypothesis for an acute exercise–cognition interaction. Pharmacology Biochemistry and Behavior, 89(1), 106–115.

6. Meeusen, R., & De Meirleir, K. (1995). Exercise and brain neurotransmission. Sports Medicine, 20(3), 160–188.

7. Robertson, C. L., Ishibashi, K., Chudzynski, J., et al. (2016). Effect of exercise training on striatal dopamine D2/D3 receptors in methamphetamine users during behavioral treatment. Neuropsychopharmacology, 41(6), 1629–1636.

8. Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015). A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor. Journal of Psychiatric Research, 60, 56–64.

9. van Praag, H., Kempermann, G., & Gage, F. H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2(3), 266–270.