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Updated: Jul 2, 2025
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Cellular iron depletion enhances behavioral rhythm by limiting brain Per1 expression in mice
Qiong Wu1,2, Qiuyang Ren1, Xin Wang1
1Laboratory of Molecular Iron Metabolism, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Collaborative Innovation Center for Eco-Environment, Hebei Research Center of the Basic Discipline of Cell Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, China.
Altered brain iron levels impact circadian rhythms by affecting PER1 expression, influencing locomotor activity and clock gene function. This research suggests brain iron regulation as a novel therapeutic target for age-related circadian disruptions.
Area of Science:
- Neuroscience
- Chronobiology
- Iron Metabolism
Background:
- Circadian rhythm disturbances are linked to aging and neurodegenerative diseases, often involving brain iron accumulation.
- The precise role of brain iron in regulating biological rhythms remains largely unexplored.
Purpose of the Study:
- To investigate how brain iron levels affect spontaneous locomotor activity in mice.
- To elucidate the underlying molecular mechanisms connecting brain iron and circadian rhythm regulation.
Main Methods:
- Utilized conditional knockout mouse models (Fpn1 in endothelial cells) to manipulate brain iron levels.
- Examined locomotor activity, clock gene expression (Clock, Bmal1, PER1), and serum melatonin.
- Investigated iron's effects on PER1 expression in human glioma (U251) and mouse cerebellar astrocyte (MA-c) cell lines in vitro.
Main Results:
- Brain iron deficiency enhanced locomotor activity and altered clock gene expression, decreasing PER1.
- Elevated brain iron in APP/PS1 mice inhibited rhythmic activity and increased serum melatonin.
- Iron levels modulated PER1 expression in both cell lines, with iron deficiency reducing PER1 and iron repletion increasing it.
Conclusions:
- Altered brain iron levels directly influence circadian rhythm by regulating PER1 expression and modulating the molecular circadian clock.
- Brain iron regulation emerges as a potential therapeutic target for age-related circadian rhythm disruptions.
