PHYSICAL ACTIVITY AND BRAIN HEALTH: “MENS SANA IN CORPORE SANO”

F. Pandolfi ^1* and R. Padula ²

¹ Allergy and Clinical Immunology, Fondazione Policlinico Universitario A, Gemelli IRCCS, Catholic University, Rome, Italy;
² Clinical and experimental biology, University of Foggia, Italy.

*Correspondence to:
Franco Pandolfi,
Allergy and Clinical Immunology,
Fondazione Policlinico Universitario A. Gemelli IRCCS,
Catholic University,
00168 Rome, Italy.
e-mail: franco.pandolfi@unicatt.it

Received: 28 March, 2024 Accepted: 20 May, 2024

2974-6345 (2024) Copyright © by BIOLIFE This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Physical activity has beneficial effects for the health of the entire body, including the central nervous system (CNS). Periodic physical exercises and consistent physical activity leads to increased cardiovascular endurance and capacity, enhanced muscular tone, increased muscular strength, improved metabolism, decreased adiposity, and additionally, strengthens the immune system, making the body less vulnerable to certain diseases. Recently, it was noticed that in physically trained subjects, the number of leukocytes was increased; this contributed to greater resistance to infections by microorganisms. An important immune protein that increases in individuals who are physically active is interleukin-1 (IL-1), which is responsible for the feverish effect, and is primarily produced by monocytic cells and lymphocytes.

KEYWORDS: physical activity, sport, immunity, IL-1, neurodegenerative, health, CNS

INTRODUCTION

It is well known that physical activity is good for the health of the entire body (1). Periodic physical exercises and consistent physical activity has benefits for our health by positively affecting cardiovascular and muscular strength and metabolism, by decreasing adiposity, and additionally, by strengthening the immune system, making the body less vulnerable to certain diseases (2).

During physical activity, fatigue can occur with activation of the sympathetic system and the hypothalamus, resulting in the release of catabolic products and inflammatory molecules, including cytokines (3). Athletes who engage in intense and prolonged physical exercise have altered neuropsychological conditions and experience the loss of bodily fluids with sweating. Intense exercise can cause the release of cortisol which is an immunosuppressive molecule, and this effect can be damaging. On the other hand, it is known that physical activity improves cognitive and brain functions and moderate exercise can strengthen the immune system (4).

The impacts of physical activity and exercise on the immune system

Starting from the general concept that white blood cells defend the body and immunize it from infectious diseases, it is easy to understand that a physiological increase of these cells can strengthen the immune system (5). It has been seen that the number of leukocytes was increased in physically trained subjects; this contributes to a greater resistance to infections by microorganisms (6). The reason for the increase in leukocytes is not clear, but there are some possible hypotheses: a) physical exercise causes a loss of extracellular fluids, resulting in a greater concentration of blood cells, and therefore, a greater number of both leukocytes and red blood cells; b) after physical exercise, there is an increase in the levels of catecholamines and adrenaline, which regulate the number of leukocytes in the blood circulation; c) the production of some hormones during physical activity can affect the pool of leukocytes in circulation (7).

The increase in white blood cells plays an important role in the body’s defense against infections, although apparently the leukocytes of athletes do not appear functionally indistinguishable from those of sedentary individuals (8). The increase in leukocytes seems to affect T lymphocytes (anti-viral and anti-tumor) more than B lymphocytes, which protect from bacterial infections (9). Another important immune element that increases in individuals who are physically active is interleukin-1 (IL-1), a protein produced by some leukocytes that is responsible for mediating fever and the inflammatory response (10).

IL-1 causes fever in humans and is responsible for producing heat in cold-blooded animals (11). Human fever is an immune reaction that serves to protect the body from insults, such as bacterial and viral infections. During the inflammatory reaction, IL-1 is produced by macrophagic cells and increases inflammation, which is detrimental to the body (12). Elevated levels of IL-1 produce fever, and a subsequent drop in blood iron levels, a reaction that protects the body from microbial invasion (13). IL-1 activates leukocytes such as lymphocytes and macrophages, which are responsible for the immune reaction.

The increase in temperature due to exercise stimulates the production of IL-1 which mediates the immune response (14). Hyperthermia after exercise depends on both the metabolic activity of the muscles and the production of IL-1 (15). In general, when the leukocytes of athletes are stimulated in vitro, they produce more IL-1 than those who do not participate in sports, and athletes are less likely to experience states of depression (16). Again, in the laboratory, by bringing the peripheral blood leukocytes of sedentary individuals into contact with the serum of athletes, cellular stimulation and greater reactivity against microorganisms were obtained (17).

IL-1 is an endogenous mediator of fever and belongs to the cytokine family composed of pleiotropic molecules that are involved in many pathological processes (18). Animals treated with IL-1 were seen to develop hypotension caused by the induction of nitric oxide (NO) and decreased systolic blood pressure (19). The cytokine IL-2 (or T cell growth factor) also causes fever with an indirect mechanism on the hypothalamus, unlike IL-1 (20). IL-2 induces IL-1, tumor necrosis factor (TNF), and interferon gamma (IFN-g), but not the marker C-reactive protein which is induced by IL-1 (21).

Physical training with an immune stimulus can be part of anti-tumor therapy without harmful effects on the body compared to conventional anti-tumor therapies which cause inflammation and immunodepression. Physical exercises reduce pro-inflammatory markers such as C-reactive protein and TNF, a potent inducer of inflammation and mediator of neuroinflammation, without inhibiting natural killer (NK) cells and cytotoxic T lymphocytes (22). However, this data still needs to be confirmed by future studies.

Different studies highlight the stimulus, albeit mild, of physical activity on NK cells, which are important for the immune response against malignant tumor diseases (23). NK cells are circulating lymphocytes that increase after physical exercise and are involved in the anti-tumor immune response with a cytotoxic effect (24). In addition, it was noted that individuals (not professional athletes) who practiced periodic exercises had a longer life expectancy than those who did not partake in physical activity (25).

The cytokines and chemokines that are involved in inflammation and could be regulated by physical activity are shown below (26) (Table I).

Table I. Cytokines and chemokines mediating inflammation that could be regulated by physical activity.

The belief that exposing the body to cold can lower its resistance to infections finds a scientific explanation in the fact that certain viruses and bacteria that habitually and harmlessly live in the organism become pathogenic when body temperature is lowered (27). Experiments and studies have clearly demonstrated that recurring physical exercises reduce the risk of cardiovascular disease and contribute to longevity. But not only that, exercise helps to keep body weight under control, increase energy, and reduce stress (28).

If adrenaline is injected into a resting individual in quantities equal to those produced by an athlete after effective physical exercise, the increase in the number of leukocytes will be the same as that of the athlete (29). This means that adrenaline, which is also one of the compounds responsible for growth (GH), is stimulated by physical activity (30). This, as is known, is co-responsible, together with other compounds, for the production of antibodies, rejection reactions, and the increase in neutrophils (31).

To date, there is no clinical evidence to demonstrate that physical exercise has anti-tumor effects, but what is certain is that physical activity increases NK cells which are capable of killing tumor cells. When the NK cells of an athlete are collected after intense physical exercise and put into contact with tumor cells in vitro, there is a greater degree of killing by the leukocytes compared to NK cells derived from individuals who do not practice sport (32). Several expert scientists, specializing in sport and immunity, have stated that vigorous and periodic physical activity provides the body with a natural defense, protecting individuals against ageing and cardiac ischemia and its consequences (33).

The impacts of physical activity and exercise on brain health

Physical activity has beneficial effects for the brain and the central nervous system (CNS) (34). Research has shown that exercise positively affects cognition, and that lack of physical activity is a risk factor for many diseases, including cardiovascular pathologies and neurodegenerative disorders (35). The immune-modifying properties of physical activity and exercise have anti-inflammatory effects throughout the entire body, including the CNS (36).

Reactive oxygen species (ROS) are produced by muscles during physical exercise and stimulate the transport of glucose necessary for an increase in metabolism (37). In the brain, there is an increase in metabolic activity as blood flow increases and ROS are produced by neuronal cells (38). The production of ROS occurs mainly in the mitochondria, and their increase could contribute to ageing (39).

A sedentary lifestyle is damaging for bodily health and cognitive and brain functions. Studies on physical activity in the elderly have shown that neurocognitive activity is enhanced by daily exercise (40). The benefits of physical activity are undeniable and clear, however, the exact mechanisms by which it benefits brain health are not completely understood.

The neurological effects of physical activity have been evaluated with magnetic resonance imaging (MRI) and neurocognitive measures (41). It seems that physical activity leads to an increase in neurotrophic factor, which helps to maintain brain volume and provide protection for neurons, and affects lipid transport and amyloid load, which can lower the risk of dementia and prevent the development of neurodegenerative diseases (42). However, it is still unclear if physical activity affects amyloid and tau protein metabolism that occurs in Alzheimer’s disease.

The benefits of exercise were also found to be relevant in children, where physical activity has been correlated with improvements in attention and cognition (43). Regular physical activity in children has positive effects on brain structure and function, enhancing attention, learning, and memory.

Furthermore, physical activity is important to prevent obesity, which is associated with an increased risk of chronic diseases, including neurological disorders, such as dementia (44). Evidence shows that obesity is associated with cognitive deficits and functional and structural changes in the brain, as well as being a risk factor for the development of Alzheimer’s disease (45).

CONCLUSIONS

When practiced regularly, moderate physical activity has many beneficial effects for the body and can help prevent the onset of vascular, inflammatory and autoimmune, and neurological diseases. In modern times, life is often sedentary which can be harmful to health, and exercise should be stressed as an important habit to maintain health of the entire body, including the brain. Further studies should continue to clarify the mechanisms by which physical activity affects the immune and neurological systems.

Conflict of interest

The authors declare that they have no conflict of interest.

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