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Astrocyte hepcidin ameliorates neuronal loss through attenuating brain iron deposition and oxidative stress in APP/PS1 mice
- Source :
- Free Radical Biology and Medicine. 158:84-95
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Iron overload in the brain and iron-induced oxidative damage have been considered to play key roles in the pathogenesis of Alzheimer's disease (AD). Hepcidin is a peptide that regulates systemic iron metabolism by interacting with iron exporter ferroportin 1 (FPN1). Studies have indicated that the astrocyte hepcidin could regulate brain iron intake at the blood-brain barrier and injection of hepcidin into brain attenuated iron deposition in the brain. However, whether overexpression of hepcidin in astrocytes of APP/PS1 transgenic mice can alleviate AD symptoms by reducing iron deposition has not been evaluated. In this study, we overexpressed hepcidin in astrocytes of APP/PS1 mice and investigated its effects on β-amyloid (Aβ) aggregation, neuronal loss, iron deposition and iron-induced oxidative damages. Our results showed that the elevated expression of astrocyte hepcidin in APP/PS1 mice significantly improved their cognitive decline, and partially alleviated the formation of Aβ plaques in cortex and hippocampus. Further investigations revealed that overexpression of hepcidin in astrocytes significantly reduced iron levels in cortex and hippocampus of APP/PS1 mice, especially iron content in neurons, which led to the reduction of iron accumulation-induced oxidative stress and neuroinflammation, and finally decreased neuronal cell death in the cortex and hippocampus of APP/PS1 mice. This study demonstrated that overexpression of hepcidin in astrocytes of APP/PS1 mice could partially alleviate AD symptoms and delay the pathological process of AD.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
medicine.medical_specialty
Programmed cell death
Iron
Hippocampus
Mice, Transgenic
medicine.disease_cause
Biochemistry
Amyloid beta-Protein Precursor
Mice
03 medical and health sciences
0302 clinical medicine
Hepcidins
Alzheimer Disease
Hepcidin
Physiology (medical)
Internal medicine
mental disorders
Presenilin-1
medicine
Animals
Cognitive decline
Neuroinflammation
Amyloid beta-Peptides
biology
Chemistry
Brain
Disease Models, Animal
Oxidative Stress
030104 developmental biology
Endocrinology
medicine.anatomical_structure
nervous system
Astrocytes
biology.protein
030217 neurology & neurosurgery
Oxidative stress
Astrocyte
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....d568ace2ad3b0783654302b68acef87a