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Aging causes brain changes that impair cognitive function, even in people who do not have Alzheimer’s disease or dementia. However, lifestyle factors like diet and exercise have significant influence over the rate of cognitive decline. Previous research has shown that exercise improves brain health and cognitive function during aging. A new report details the role of the muscle hormone irisin in the neuroprotective effects of exercise
Irisin, a type of myokine, is a hormone secreted from muscle in response to exercise. Previous research has shown that irisin may mediate some of the beneficial effects of exercise on the brain by stimulating the production of brain-derived neurotrophic factor (BDNF), a growth factor that increases neuroplasticity. Irisin is a fragment of the prohormone FNDC5, which is attached to the membranes of muscle cells. During exercise, irisin is cleaved from FNDC5 and circulates throughout the body to induce adaptations to exercise.
The authors used mice of varying ages who lack the genes necessary to produce FNDC5, called knock-outs, and genetically-normal mice, called wild-type. Both groups of mice completed exercise testing to measure balance, grip strength, endurance, and motor coordination; a water maze test to measure spatial learning ability and memory; and an open field test to measure locomotor activity levels, anxiety, and willingness to explore. In order to study the effects of irisin supplementation, the investigators conducted a second experiment in which they administered exogenous (i.e., made outside the body) irisin to a strain of mice who develop an Alzherimer’s-like dementia at an early age due to loss of FNDC5 function. The investigators measured structural and psychological changes in the brain throughout both experiments.
Both knock-out and wild-type mice exercised the same amount during testing. However, unlike the wild-type mice, knock-out mice did not show exercise-induced improvements in spatial learning and memory. Aged knock-out mice had more cognitive decline than wild-type mice and were less likely to prefer novel objects, a behavior associated with loss of function in the hippocampus, the brain region most associated with memory loss in dementia. Indeed, aged knock-out mice showed abnormal neuronal activation patterns in the dentate gyrus, a structure within the hippocampus that contributes to memory formation.
In contrast to knock-out mice and sedentary wild-type mice, wild-type mice who exercised had increased dendritic complexity and length in the dentate gyrus. This demonstrates the ability of exercise to improve neuronal structure and function in brain areas associated with memory through mechanisms involving irisin. Regular injections with exogenous irisin significantly improved performance on spatial learning and memory tasks in mice with Alzheimer’s-like dementia compared to untreated mice. These improvements may have been caused by dampening of overactive glial activity, leading to reduced inflammation.
Taken together, these data suggest that irisin is essential for mediating the beneficial effects of exercise on cognitive function. The authors concluded that these data also demonstrate the efficacy of exogenous irisin administration in regulating cognitive function in mice with Alzheimer’s-like dementia, providing support for future use of irisin therapies in humans with dementia.
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