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

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

Belaya, I Kucháriková, N Górová, V Kysenius, K Hare, DJ Crouch, PJ Malm, T Atalay, M White, AR Liddell, JR Kanninen, KM

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: International Journal of Molecular Sciences, 2021, 22, (16), pp. 1-17
Issue Date:: 2021-08-13

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Field	Value	Language
dc.contributor.author	Belaya, I
dc.contributor.author	Kucháriková, N
dc.contributor.author	Górová, V
dc.contributor.author	Kysenius, K
dc.contributor.author	Hare, DJ
dc.contributor.author	Crouch, PJ
dc.contributor.author	Malm, T
dc.contributor.author	Atalay, M
dc.contributor.author	White, AR
dc.contributor.author	Liddell, JR
dc.contributor.author	Kanninen, KM
dc.date.accessioned	2022-02-14T01:18:49Z
dc.date.available	2021-08-09
dc.date.available	2022-02-14T01:18:49Z
dc.date.issued	2021-08-13
dc.identifier.citation	International Journal of Molecular Sciences, 2021, 22, (16), pp. 1-17
dc.identifier.issn	1422-0067
dc.identifier.issn	1422-0067
dc.identifier.uri	http://hdl.handle.net/10453/154475
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	International Journal of Molecular Sciences
dc.relation.isbasedon	10.3390/ijms22168715
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences
dc.subject.classification	Chemical Physics
dc.subject.mesh	Alzheimer Disease
dc.subject.mesh	Animals
dc.subject.mesh	Brain
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Exercise
dc.subject.mesh	Gene Expression Regulation
dc.subject.mesh	Hepcidins
dc.subject.mesh	Homeostasis
dc.subject.mesh	Humans
dc.subject.mesh	Interleukin-6
dc.subject.mesh	Iron
dc.subject.mesh	Male
dc.subject.mesh	Mass Spectrometry
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Muscle, Skeletal
dc.subject.mesh	Sedentary Behavior
dc.subject.mesh	Muscle, Skeletal
dc.subject.mesh	Brain
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Transgenic
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Alzheimer Disease
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Iron
dc.subject.mesh	Interleukin-6
dc.subject.mesh	Exercise
dc.subject.mesh	Gene Expression Regulation
dc.subject.mesh	Homeostasis
dc.subject.mesh	Male
dc.subject.mesh	Mass Spectrometry
dc.subject.mesh	Hepcidins
dc.subject.mesh	Sedentary Behavior
dc.title	Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease
dc.type	Journal Article
utslib.citation.volume	22
utslib.location.activity	Switzerland
utslib.for	0399 Other Chemical Sciences
utslib.for	0604 Genetics
utslib.for	0699 Other Biological Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-02-14T01:18:44Z
pubs.issue	16
pubs.publication-status	Published
pubs.volume	22
utslib.citation.issue	16

Abstract:

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.

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http://hdl.handle.net/10453/154475