Astrocyte hepcidin ameliorates neuronal loss through attenuating brain iron deposition and oxidative stress in APP/PS1 mice
| Autor: | Yan-Zhong Chang, Xue Bai, Guofen Gao, Peng Yu, Jian-Hua Zhang, Kang Han, Yong Xu, Zhenhua Shi, Yating Zhang, Linhao You, Xinwei Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Free Radical Biology and Medicine. 158:84-95 |
| ISSN: | 0891-5849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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