Summary: Regular exercise modulates iron storage and trafficking in the brain and skeletal muscles, and physical activity reduces cortical hepcidin. The findings reveal how exercise can be beneficial for those with Alzheimer’s disease.
Source: University of Eastern Finland
A recent experimental study shows how regular physical exercise modulates iron metabolism in both the brain and the muscles. The findings 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 entitled Redox Active Metals in Neurodegenerative Diseases: Therapeutic Implications.
Dysregulation of brain iron metabolism and iron accumulation is known to be associated with ageing and AD, although underlying mechanisms remain unclear. 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.
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.
The study was conducted in the Neurobiology of Disease laboratory led by Associate Professor Katja Kanninen at the University of Eastern Finland.
Funding: The study was supported by the Academy of Finland, the Sigrid Juselius foundation, the Finnish Cultural Foundation, and the University of Eastern Finland.
About this exercise and Alzheimer’s disease research news
Author: Ulla Kaltiala Source: University of Eastern Finland Contact: Ulla Kaltiala – University of Eastern Finland Image: The image is in the public domain
Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease
Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment.
While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear.
The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice.
Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle.
Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway.
These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.