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年龄、受教育年限和生化因素与老年人海马体的选择性神经元变化有关。

Age, Education Years, and Biochemical Factors Are Associated with Selective Neuronal Changes in the Elderly Hippocampus.

机构信息

Graduate Program in Neuroengineering, Edmond and Lily Safra International Institute of Neuroscience, Santos Dumont Institute, Macaíba 59280-000, Brazil.

出版信息

Cells. 2022 Dec 13;11(24):4033. doi: 10.3390/cells11244033.

Abstract

Brain aging involves regional alterations of specific cellular subpopulations in the human hippocampus: a network hub for memory consolidation. The present study investigates whether age, sex, education years, and the concentration of neuropathological and inflammatory proteins influence neuronal-type marker expression in the elderly hippocampus. We analyzed the digital images (1 µm/pixel) of postmortem hippocampal sections from 19 non-demented individuals (from 78 to 99 years). This material was obtained from the "Aging Dementia and TBI Study" open database. Brain samples were processed through in situ hybridization (ISH) for the immunodetection of VGLUT1 (glutamatergic transporter) and GAT1 (GABAergic transporter) and mRNAs and Luminex protein quantifications. After image acquisition, we delineated the dentate gyrus, CA 3/2, and CA1 hippocampal subdivisions. Then, we estimated the area fraction in which the ISH markers were expressed. Increased VGLUT1 was observed in multiple hippocampal subfields at late ages. This glutamatergic marker is positively correlated with beta-amyloid and tau proteins and negatively correlated with interleukin-7 levels. Additionally, education years are positively correlated with GAT1 in the hippocampus of elderly women. This GABAergic marker expression is associated with interferon-gamma and brain-derived neurotrophic factor levels. These associations can help to explain how hippocampal sub-regions and neurotransmitter systems undergo distinct physiological changes during normal aging.

摘要

大脑老化涉及人类海马体特定细胞亚群的区域性改变

记忆巩固的网络中枢。本研究调查了年龄、性别、受教育年限以及神经病理和炎症蛋白的浓度是否会影响老年海马体中的神经元型标志物表达。我们分析了 19 名无痴呆个体(年龄 78 至 99 岁)死后海马体切片的数字图像(1 µm/pixel)。这些材料来自“衰老痴呆和 TBI 研究”开放数据库。通过原位杂交(ISH)对脑样本进行处理,以免疫检测 VGLUT1(谷氨酸转运体)和 GAT1(GABA 转运体)和 mRNAs,并进行 Luminex 蛋白定量。在获取图像后,我们描绘了齿状回、CA3/2 和 CA1 海马亚区。然后,我们估计了ISH 标志物表达的面积分数。在晚期,多个海马亚区观察到 VGLUT1 增加。这种谷氨酸能标志物与β-淀粉样蛋白和 tau 蛋白呈正相关,与白细胞介素-7 水平呈负相关。此外,教育年限与老年女性海马体中的 GAT1 呈正相关。这种 GABA 能标志物的表达与干扰素-γ和脑源性神经营养因子水平相关。这些关联可以帮助解释海马体亚区和神经递质系统在正常衰老过程中如何发生不同的生理变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5697/9777473/1bc215b83c44/cells-11-04033-g0A1.jpg

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