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Interoceptive Signaling by Circulating Insulin Like Growth Factor I and Neuroprotection by Exercise.
Jonathan Zegarra-Valdivia1,2,3,4, Estrella Fernandez de Sevilla2,5, Jaime Pignatelli2,5
1Achucarro Basque Center for Neuroscience, Leioa, Spain.
Advances in Neurobiology
|September 26, 2025
Summary
Exercise enhances brain function by increasing insulin-like growth factor I (IGF-I) in the brain. This neuroprotective signal aids cognitive function, mood, and brain repair, offering therapeutic potential for neurological diseases.
Area of Science:
- Neuroscience
- Exercise Physiology
- Molecular Biology
Background:
- Physical activity benefits brain function and is a favored approach for preventing and treating neurological diseases.
- Lack of effective therapies for brain diseases necessitates research into exercise's neuroprotective mechanisms.
- Pharmacological mimics of exercise's molecular pathways are of therapeutic interest for non-ambulatory patients.
Purpose of the Study:
- To examine the role of insulin-like growth factor I (IGF-I) in mediating the neuroprotective effects of exercise.
- To understand how exercise stimulates circulating IGF-I entry into the brain.
- To explore IGF-I's contribution to exercise-induced pro-neurogenic, pro-cognitive, and mood-modulatory effects.
Main Methods:
- Review of existing literature on exercise, neuroprotection, and IGF-I.
- Analysis of cellular and molecular mechanisms linking physical activity to brain health.
- Postulation of IGF-I as a humoral interoceptive signal informing the brain of muscle/bone mass.
Main Results:
- Exercise stimulates the brain's uptake of circulating IGF-I.
- IGF-I mediates exercise-induced pro-neurogenic, pro-cognitive, and mood-enhancing effects.
- IGF-I exhibits cytoprotective actions (anti-apoptotic, anti-oxidant, anti-inflammatory), supporting brain repair and homeostasis.
Conclusions:
- Circulating IGF-I is a key mediator of exercise's brain-wide neuroprotective benefits.
- IGF-I acts as an interoceptive signal, linking muscle/bone mass to brain function and physical activity.
- Understanding IGF-I's role opens avenues for therapeutic strategies mimicking exercise benefits for neurological conditions.
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