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Exercise hormone irisin is a critical regulator of cognitive function.
Mohammad R Islam1, Sophia Valaris1, Michael F Young1
1Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nature Metabolism
|August 21, 2021
Summary
Irisin, a protein linked to exercise, improves cognitive function and brain health. This discovery offers new therapeutic potential for age-related cognitive decline and Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Endocrinology
- Gerontology
Background:
- Exercise is known to benefit cognitive function, but the underlying molecular mechanisms remain incompletely understood.
- Identifying specific mediators responsible for these benefits is crucial for developing treatments for cognitive decline.
- Alzheimer's disease (AD) and aging are associated with significant cognitive impairment, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of irisin, a circulating form of FNDC5, in mediating the cognitive benefits of exercise.
- To determine if irisin is sufficient to confer exercise-induced cognitive improvements and to explore its therapeutic potential in AD.
- To elucidate the effects of irisin deficiency and supplementation on neurogenesis and cognitive function in aging and AD models.
Main Methods:
- Utilized global Fndc5 knock-out (KO) mice (F5KO) to study the effects of irisin deficiency on cognitive function.
- Administered irisin directly into the dentate gyrus and via peripheral delivery (adeno-associated viral overexpression in the liver) in mouse models.
- Assessed cognitive performance, pattern separation, and the morphology, transcriptional profile, and function of adult-born neurons in the dentate gyrus.
Main Results:
- Genetic deletion of Fndc5/irisin impaired cognitive function in exercise, aging, and AD contexts.
- Direct delivery of irisin rescued diminished pattern separation in F5KO mice, confirming irisin as the active moiety.
- Peripheral irisin elevation improved cognitive deficits and neuropathology in AD mouse models, with enriched central irisin levels.
Conclusions:
- Irisin is a critical regulator of the cognitive benefits associated with exercise.
- Irisin plays a significant role in maintaining cognitive function during aging and in the context of Alzheimer's disease.
- Irisin demonstrates potential as a therapeutic agent for treating cognitive disorders, including AD.
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