It is known that iron load and inflammation 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 the activation of hepcidin synthesis in the brain.

‘Modulation of iron metabolism in both the brain and the muscles may occur due to through regular physical exercise. ’


Although regular physical exercise is known to have a beneficial effect on total body iron metabolism and anti-inflammatory action, the role of regular exercise on iron homeostasis in the brain and in the context of AD remains unclear.

The researchers utilised wildtype mice and 5xFAD transgenic mice, modelling AD to explore the effect of regular physical exercise on the modulation of iron homeostasis. Half of the mice had unlimited use of a running wheel during the six-month experiment.

The levels of iron and iron-related proteins were analysed in the brain and skeletal muscle. The researchers also investigated the potential involvement of iron in the crosstalk between the brain and periphery upon regular exercise.

The current study demonstrates that regular physical exercise modulates iron storage and trafficking in both the brain and skeletal muscle. Moreover, this study is the first to report a reduction of cortical hepcidin in response to regular physical exercise.

The results suggest that IL-6 is a key modulator of hepcidin in exercise-induced brain iron modulation. These findings help to better understand why regular exercise is beneficial in AD, and may provide new insight for disease prevention or effective treatment approaches.

Source: Medindia

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