Need a Dose of Hope? Give Yourself a Hope Boost by Engaging in Movement

The Role of Skeletal Muscle as a Hormone-Producing Organ and Releaser of “Hope Molecules”

While the benefits of muscle-induced exercise are well known, little discussion is explicitly made of skeletal muscle’s role in mental health and as a hormone-producing organ. Skeletal muscle secretes hundreds of signaling protein molecules (600+) called myokines that serve as communication agents between muscles and other organs in the body such as the brain, bone, liver, gut, vascular bed, pancreas, and skin (1)(2)(3)(4).

While the positive effect of physical activity on mental health has been experienced by many, it was not until recent years that our understanding of the underlying mechanisms by which exercise impacts mental health and cognitive function has been elucidated. Today, we are learning about the extraordinary interdependence of the musculoskeletal and central nervous systems (brain and spinal cord). These systems coordinate, collaborate, and support each other’s functions via molecular communication mechanisms related to our overarching mental health and brain activity (5).

Mounting research reflects physical activity’s positive health benefits, particularly concerning brain health. Mind-altering effects of movement help to improve cognitive function, decrease risks for dementia, and lower depressive symptoms through the creation of a muscle-brain cycle (endocrine loop) (2)(6).

The brain can indirectly sense exercise via peripheral factors within the liver and adipose (fat) tissue and by myokine release into the bloodstream for direct communication between muscle and the brain (6). A 2018 study showed that completing just one hour of cycling exercise in healthy subjects generated over 300 proteins into circulation (7). Therefore, movement is considered an agent by which the brain can remodel itself and acknowledge one’s aliveness and participation in life. 

Specific myokines cross the blood-brain barrier to enhance processes enabling new nerve cell formation (neurogenesis), memory, and learning. While other myokines alter the chemical balance reducing depression-like systems (6). By inducing movement, skeletal muscle is identified as a mechanism that reduces the detrimental effects of stress, augments resiliency to depression, and provides a hopeful mindset (8).

Considered muscular-secreted hormones, myokines may serve as a novel therapeutic intervention, not only for chronic diseases mitigation associated with sedentary lifestyles, but also for good mental health (1). With rising rates of depression, active muscle engagement through moderate exercise is one way to provide mental health support (3). Robust evidence has shown that exercise can be considered an evidence-based treatment for the management of depression (9) (10). 

Upon release, myokines appear to function as molecular mediators having whole-body effects upon exercising (1). Typically in our health education courses, we are introduced to some of the body’s primary internal systems, such as circulatory and cardiovascular systems. Yet other less-known systems, such as the body’s internal communication systems, which are incredibly vital to our physical, mental, and emotional health, are less frequently discussed. If we can begin to think in terms of the various “communication and signaling pathways” transpiring between body systems, it may be easier to understand the influences our actions and patterns have on our holistic health and wellness. 

Our bodies reward us with pleasure, joy, and hope upon movement. Our physiology nudges us to keep moving by rewarding us with beneficial molecules, peptides, and hormones that amplify elevated emotions and propel our purpose, resiliency, and energy. We have an internal pharmacy within our amazing bodies, and understanding how to activate and influence these natural processes is paramount to our mental, physical, and emotional health.

 Key Points and Call-To-Action

1.  Movement and mental health are inextricably connected.

2. “Hope molecules” known as myokines are produced and released by skeletal muscles upon movement.

3. Some myokines can cross the blood-brain barrier, directly communicating and influencing the brain’s activity and function.

4. Our bodies were meant to move, and our physiologies support movement through the inner pharmacy’s release of beneficial peptides/hormones.

5. Aerobic exercise and physical activity are evidence-based methods to manage depression. Exercise is as effective as antidepressant use in many cases; however, in severe depression, exercise alone may not be enough and require adjunct treatments (11).

6. The body has an indwelling communication system and speaks in the language of cellular signaling and energetic conductions (12).

Reference:

1. Schnyder S, Handschin C. Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise. Bone. 2015;80:115-125. doi:10.1016/j.bone.2015.02.008

2. Severinsen MCK, Pedersen BK. Muscle-Organ Crosstalk: The Emerging Roles of Myokines [published correction appears in Endocr Rev. 2021 Jan 28;42(1):97-99]. Endocr Rev. 2020;41(4):594-609. doi:10.1210/endrev/bnaa016

3. McGee SL, Hargreaves M. Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit. Nat Rev Endocrinol. 2020;16(9):495-505. doi:10.1038/s41574-020-0377-1

4. Lee JH, Jun HS. Role of Myokines in Regulating Skeletal Muscle Mass and Function. Front Physiol. 2019;10:42. Published 2019 Jan 30. doi:10.3389/fphys.2019.00042

5. Phillips C, Salehi A. A Special Regenerative Rehabilitation and Genomics Letter: Is There a "Hope" Molecule?. Phys Ther. 2016;96(4):581-583. doi:10.2522/ptj.2016.96.4.581

6. Pedersen BK. Physical activity and muscle-brain crosstalk. Nat Rev Endocrinol. 2019;15(7):383-392. doi:10.1038/s41574-019-0174-x

7. Whitham M, Parker BL, Friedrichsen M, et al. Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise. Cell Metab. 2018;27(1):237-251.e4. doi:10.1016/j.cmet.2017.12.001

8. Agudelo LZ, Femenía T, Orhan F, et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell. 2014;159(1):33-45. doi:10.1016/j.cell.2014.07.051

9. Schuch FB, Vancampfort D, Richards J, Rosenbaum S, Ward PB, Stubbs B. Exercise as a treatment for depression: A meta-analysis adjusting for publication bias. J Psychiatr Res. 2016;77:42-51. doi:10.1016/j.jpsychires.2016.02.023

10. Morres ID, Hatzigeorgiadis A, Stathi A, et al. Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta-analysis. Depress Anxiety. 2019;36(1):39-53. doi:10.1002/da.22842

11. https://www.health.harvard.edu/mind-and-mood/exercise-is-an-all-natural-treatment-to-fight-depression

12. Jastremski, H. Bright Heart Wellness Newsletter, 2022. “Have You Fired Up Those Muscles Today? You May Have Accomplished More Than Muscular Burn and Fatigue: The Role of Exercise Metabolite Lactate in Brain Function and Mental Health” 

Have You Fired Up Those Muscles Today?

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**As always, please consult your physician before making changes to your health regimen. The information provided is for educational and informative purposes only and is not intended for treatment or diagnosis.

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