Exercise modulates iron in Alzheimer’s disease

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A recent experimental study shows how regular physical exercise modulates iron metabolism in the brain and muscles. The results also help to better understand the benefits of exercise in Alzheimer’s disease. The study was published in a special issue of the International Journal of Molecular Sciences titled Redox Active Metals in Neurodegenerative Diseases: Therapeutic Implications.

Deregulation of brain iron metabolism and iron accumulation are known to be associated with aging and AD, although the underlying mechanisms remain unclear. Iron loading and inflammation are known to regulate the synthesis of hepcidin, the main iron regulatory protein. In particular, the inflammation-modulating cytokine interleukin-6 (IL-6), also known to modulate brain-muscle crosstalk, is involved in activating hepcidin synthesis in the brain. Although regular physical exercise is known to have a beneficial effect on total body iron metabolism and anti-inflammatory action, the role of regular physical exercise on iron homeostasis in the brain and in the background of AD remains uncertain.

The researchers used wild-type mice and 5xFAD transgenic mice, modeling AD to explore the effect of regular exercise on the modulation of iron homeostasis. Half of the mice had unlimited use of a running wheel during the six-month experiment. Levels of iron and related proteins were analyzed in the brain and skeletal muscle. The researchers also investigated the potential involvement of iron in crosstalk between the brain and the periphery during regular exercise.

The present study shows that regular physical exercise modulates the storage and trafficking of iron in the brain and skeletal muscles. In addition, this study is the first to report a reduction in cortical hepcidin in response to regular exercise. The results suggest that IL-6 is a key modulator of hepcidin in exercise-induced modulation of brain iron. These findings help to better understand why regular exercise is beneficial in AD and may provide new insights for disease prevention or effective treatment approaches.

The study was conducted in the Laboratory of Neurobiology of Diseases headed by Associate Professor Katja Kanninen at the University of Eastern Finland. The study was supported by the Academy of Finland, the Sigrid Juselius Foundation, the Finnish Cultural Foundation and the University of Eastern Finland.

Source: University of Eastern Finland


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