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Article

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

1
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland
2
Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, VIC 3010, Australia
3
School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia
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Atomic Medicine Initiative, University of Technology Sydney, Sydney, NSW 2007, Australia
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Institute of Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland
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Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Athanasios Salifoglou
Int. J. Mol. Sci. 2021, 22(16), 8715; https://doi.org/10.3390/ijms22168715
Received: 30 June 2021 / Revised: 2 August 2021 / Accepted: 9 August 2021 / Published: 13 August 2021
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. View Full-Text
Keywords: Alzheimer’s disease; 5xFAD mouse; regular voluntary exercise; iron; hepcidin; il-6; cortex; skeletal muscle Alzheimer’s disease; 5xFAD mouse; regular voluntary exercise; iron; hepcidin; il-6; cortex; skeletal muscle
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MDPI and ACS Style

Belaya, I.; Kucháriková, N.; Górová, V.; Kysenius, K.; Hare, D.J.; Crouch, P.J.; Malm, T.; Atalay, M.; White, A.R.; Liddell, J.R.; Kanninen, K.M. Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2021, 22, 8715. https://doi.org/10.3390/ijms22168715

AMA Style

Belaya I, Kucháriková N, Górová V, Kysenius K, Hare DJ, Crouch PJ, Malm T, Atalay M, White AR, Liddell JR, Kanninen KM. Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2021; 22(16):8715. https://doi.org/10.3390/ijms22168715

Chicago/Turabian Style

Belaya, Irina, Nina Kucháriková, Veronika Górová, Kai Kysenius, Dominic J. Hare, Peter J. Crouch, Tarja Malm, Mustafa Atalay, Anthony R. White, Jeffrey R. Liddell, and Katja M. Kanninen 2021. "Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease" International Journal of Molecular Sciences 22, no. 16: 8715. https://doi.org/10.3390/ijms22168715

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