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

International Journal of Molecular Sciences

Nina Kucháriková¹  Tarja Malm¹  Irina Belaya¹  Veronika Górová¹  Katja M. Kanninen¹  Peter J. Crouch²  Jeffrey R. Liddell²  Kai Kysenius²  Mustafa Atalay³  Anthony R. White⁴  Dominic J. Hare⁵ 

[1] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland;Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, VIC 3010, Australia;Institute of Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland;Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia;School of BioSciences, The University of Melbourne, Melbourne, VIC 3010, Australia;

关键词: Alzheimer’s disease;    5xFAD mouse;    regular voluntary exercise;    iron;    hepcidin;    il-6;   

DOI  :  10.3390/ijms22168715

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown