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乳铁蛋白受体(LfR)在脑不同区域对乳铁蛋白干预的分子特征及表达

Molecular Characterization and Expression of Lactoferrin Receptor (LfR) in Different Regions of the Brain Responding to Lactoferrin Intervention.

作者信息

Wang Siqi, Zhang Nai, Jiang Bowen, Lönnerdal Bo, Chen Yue, Wang Bing

机构信息

School of Medicine, Xiamen University, Xiamen City, 361102, China.

Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.

出版信息

Mol Neurobiol. 2025 Mar;62(3):2857-2871. doi: 10.1007/s12035-024-04378-z. Epub 2024 Aug 24.

DOI:10.1007/s12035-024-04378-z
PMID:39179683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11790811/
Abstract

Lactoferrin (LF), an iron-binding glycoprotein rich in human milk, promotes neurodevelopment and cognition, but whether it acts through the LF receptor (LfR) and its expression profile in the brain remains unknown. We characterized 972 bp of piglet brain LfR cDNA and found LfR mRNA was expressed all brain regions being highest in the frontal lobe, followed by parietal lobe, brainstem, occipital lobe, cingulate gyrus, subventricular zone, olfactory bulb, hippocampus, amygdala, cerebellum, and thalamus. LfR mRNA and protein in different regions of the brain responded to low (155 mg/kg/day) and high (285 mg/kg/day) LF supplementation of piglets from postnatal days 3 to 38. By postnatal day 39, the low LF diet significantly increased LfR protein expression in the occipital lobe compared to controls, but not the high LF diet. LfR protein in the subventricular zone of the high LF group was 42% and 38% higher than that of the low LF group and controls, respectively. There was a trend for a dose-response relationship between LF intervention and LfR protein expression only in the prefrontal and parietal lobes. LF supplementation significantly improved piglet working memory for a difficult task, which was positively correlated with LfR protein in the prefrontal, parietal, and occipital lobes, but no dose response. Brain LfR responds to dietary LF supplementation, a mechanism by which LF can promote learning and working memory through its receptor. LfR is expressed in the whole brain, and its expression level is anatomic region specific.

摘要

乳铁蛋白(LF)是一种富含于人乳中的铁结合糖蛋白,可促进神经发育和认知,但它是否通过乳铁蛋白受体(LfR)发挥作用及其在大脑中的表达谱仍不清楚。我们对仔猪脑LfR cDNA的972 bp进行了表征,发现LfR mRNA在所有脑区均有表达,额叶中表达最高,其次是顶叶、脑干、枕叶、扣带回、脑室下区、嗅球、海马体、杏仁核、小脑和丘脑。从出生后第3天到38天,仔猪不同脑区的LfR mRNA和蛋白对低剂量(155 mg/kg/天)和高剂量(285 mg/kg/天)的LF补充有反应。到出生后第39天,低LF饮食组枕叶中的LfR蛋白表达与对照组相比显著增加,但高LF饮食组没有。高LF组脑室下区的LfR蛋白分别比低LF组和对照组高42%和38%。仅在额叶和顶叶中,LF干预与LfR蛋白表达之间存在剂量反应关系趋势。补充LF显著改善了仔猪完成困难任务的工作记忆,这与额叶、顶叶和枕叶中的LfR蛋白呈正相关,但不存在剂量反应。脑LfR对饮食中LF补充有反应,这是LF通过其受体促进学习和工作记忆的一种机制。LfR在全脑中表达,其表达水平具有解剖区域特异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83a1/11790811/e10ddb9fa989/12035_2024_4378_Fig7_HTML.jpg
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本文引用的文献

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Nutrients. 2022 Jul 17;14(14):2923. doi: 10.3390/nu14142923.
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Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia.乳铁蛋白诱导缺氧孕鼠子代红细胞生成素合成和挽救认知功能。
Nutrients. 2022 Mar 27;14(7):1399. doi: 10.3390/nu14071399.
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Dose-Dependent Neuroprotective Effects of Bovine Lactoferrin Following Neonatal Hypoxia-Ischemia in the Immature Rat Brain.
牛乳铁蛋白对新生大鼠缺氧缺血性脑损伤的剂量依赖性神经保护作用。
Nutrients. 2021 Oct 29;13(11):3880. doi: 10.3390/nu13113880.
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Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.内皮细胞特异性 LRP1 耗竭通过诱导骨钙素改善葡萄糖稳态。
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Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19.乳铁蛋白对心理健康的作用:通过血脑屏障的神经氧化还原调节和神经保护作用,特别提及神经型冠状病毒病(Neuro-COVID-19)
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