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阿尔茨海默病成年神经发生模型中的 NXN 基因表观遗传变化。

NXN Gene Epigenetic Changes in an Adult Neurogenesis Model of Alzheimer's Disease.

机构信息

Neuroepigenetics Laboratory-Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA (Navarra Institute for Health Research), 31008 Pamplona, Spain.

CIBIR (Center for Biomedical Research of La Rioja), 26006 Logroño, Spain.

出版信息

Cells. 2022 Mar 22;11(7):1069. doi: 10.3390/cells11071069.

DOI:10.3390/cells11071069
PMID:35406633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8998146/
Abstract

In view of the proven link between adult hippocampal neurogenesis (AHN) and learning and memory impairment, we generated a straightforward adult neurogenesis model to recapitulate DNA methylation marks in the context of Alzheimer's disease (AD). Neural progenitor cells (NPCs) were differentiated for 29 days and Aβ peptide 1-42 was added. mRNA expression of Neuronal Differentiation 1 (), Neural Cell Adhesion Molecule 1 (), Tubulin Beta 3 Class III (), RNA Binding Fox-1 Homolog 3 (), Calbindin 1 (), and Glial Fibrillary Acidic Protein () was determined by RT-qPCR to characterize the culture and framed within the multistep process of AHN. Hippocampal DNA methylation marks previously identified in Contactin-Associated Protein 1 (), SEPT5-GP1BB Readthrough (), T-Box Transcription Factor 5 (), and Nucleoredoxin () genes were profiled by bisulfite pyrosequencing or bisulfite cloning sequencing; mRNA expression was also measured. outlined a peak of DNA methylation overlapping type 3 neuroblasts. Aβ-treated NPCs showed transient decreases of mRNA expression for and on day 9 or 19 and an increase in DNA methylation on day 29 for . and may reflect alterations detected in the brain of AD human patients, broadening our understanding of this disease.

摘要

鉴于成人海马神经发生 (AHN) 与学习和记忆障碍之间的已知关联，我们生成了一个简单的成人神经发生模型，以重现阿尔茨海默病 (AD) 背景下的 DNA 甲基化标记。神经祖细胞 (NPC) 分化 29 天，并添加 Aβ 肽 1-42。通过 RT-qPCR 测定神经元分化 1 ()、神经细胞黏附分子 1 ()、微管β 3 类 III ()、RNA 结合 Fox-1 同源物 3 ()、钙结合蛋白 1 () 和神经胶质纤维酸性蛋白 () 的 mRNA 表达，以表征培养物，并框定在 AHN 的多步过程中。通过亚硫酸氢盐焦磷酸测序或亚硫酸氢盐克隆测序对先前在接触蛋白相关蛋白 1 ()、SEPT5-GP1BB 通读 ()、T 盒转录因子 5 () 和核还原蛋白 () 基因中鉴定的海马 DNA 甲基化标记进行分析；还测量了 mRNA 表达。结果表明，DNA 甲基化峰与 3 型神经母细胞重叠。Aβ 处理的 NPC 在第 9 天或第 19 天表现出 和 的 mRNA 表达短暂下降，而 在第 29 天的 DNA 甲基化增加。和 可能反映了在 AD 人类患者大脑中检测到的改变，从而拓宽了我们对这种疾病的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/3285bc2322ea/cells-11-01069-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/f20e77ba57c5/cells-11-01069-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/f20e77ba57c5/cells-11-01069-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/3b459741b88b/cells-11-01069-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/c39cb1458991/cells-11-01069-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/681fdc1bc24a/cells-11-01069-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/f50ead29a628/cells-11-01069-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c7/8998146/3285bc2322ea/cells-11-01069-g010.jpg

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