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Estrogen deficiency is associated with brain iron deposition via upregulation of hepcidin expression in aged female mice
Neurobiology of Aging ( IF 3.7 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.neurobiolaging.2020.08.010
Jin A Shin 1 , Hee-Sun Kim 2 , Jihee Lee Kang 3 , Eun-Mi Park 1
Affiliation  

The total iron level in the brain increases with age, and excess iron is associated with neurodegenerative diseases; however, the mechanism of brain iron deposition is unknown. In peripheral cells, the expression of hepcidin, a master regulator of iron homeostasis, is regulated by estrogen. This study aimed to determine whether hepcidin was involved in iron deposition in the brain and brain endothelial cells of estrogen-deficient aged female mice. Aged mice showed increased levels of hepcidin and ferritin in the brain and brain microvessels compared with young mice, and these levels were reduced by estrogen replacement in ovariectomized aged mice. In the brain endothelial cell line bEnd.3, the lipopolysaccharide (10 ng/mL)-induced increases of hepcidin mRNA and protein levels, the number of Prussian blue-positive cells, and free radicals were reduced after estrogen treatment. These results suggest that estrogen deficiency with an increase of hepcidin is partly responsible for iron deposition in the brain and brain endothelial cells and that hepcidin can be a target to prevent brain aging and neurodegeneration in postmenopausal women.

中文翻译:

通过上调老年雌性小鼠的铁调素表达,雌激素缺乏与脑铁沉积有关

大脑中的总铁含量随着年龄的增长而增加,过量的铁与神经退行性疾病有关;然而,脑铁沉积的机制尚不清楚。在外周细胞中,铁调素(铁稳态的主要调节剂)的表达受雌激素的调节。本研究旨在确定铁调素是否与缺乏雌激素的老年雌性小鼠的大脑和脑内皮细胞中的铁沉积有关。与年轻小鼠相比,老年小鼠的大脑和脑微血管中的铁调素和铁蛋白水平升高,而在切除卵巢的老年小鼠中,雌激素替代降低了这些水平。在脑内皮细胞系 bEnd.3 中,脂多糖 (10 ng/mL) 诱导铁调素 mRNA 和蛋白质水平增加,普鲁士蓝阳性细胞数量增加,雌激素治疗后自由基减少。这些结果表明,随着铁调素增加的雌激素缺乏是大脑和脑内皮细胞中铁沉积的部分原因,并且铁调素可以成为预防绝经后妇女大脑老化和神经变性的靶点。
更新日期:2020-12-01
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