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衰老大脑中星形胶质细胞标志物的复杂和区域特异性变化。

Complex and region-specific changes in astroglial markers in the aging brain.

机构信息

IKERBASQUE, Basque Foundation for Science, Bilbao, Spain; Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, Leioa, Spain.

出版信息

Neurobiol Aging. 2014 Jan;35(1):15-23. doi: 10.1016/j.neurobiolaging.2013.07.002. Epub 2013 Aug 19.

DOI:10.1016/j.neurobiolaging.2013.07.002
PMID:23969179
Abstract

Morphological aging of astrocytes was investigated in entorhinal cortex (EC), dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial profiles were visualized by immunohistochemistry by using glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and s100β staining; these profiles were imaged using confocal or light microscopy for subsequent morphometric analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed progressive age-dependent hypertrophy, as indicated by an increase in surface, volume, and somata volume at 24 months of age compared with 3-month-old mice. In contrast with the hippocampal regions, aging induced a decrease in GFAP-positive astroglial profiles in the EC: the surface, volume, and cell body volume of astroglial cells at 24 months of age were decreased significantly compared with the 3-month group. The GS-positive astrocytes displayed smaller cellular surface areas at 24 months compared with 3-month-old animals in both areas of hippocampus, whereas GS-positive profiles remained unchanged in the EC of old mice. The morphometry of s100β-immunoreactive profiles revealed substantial increase in the EC, more moderate increase in the DG, and no changes in the CA1 area. Based on the morphological analysis of 3 astroglial markers, we conclude that astrocytes undergo a complex age-dependent remodeling in a brain region-specific manner.

摘要

星形胶质细胞的形态老化在不同年龄组(3、9、18 和 24 个月)雄性 SV129/C57BL6 小鼠的内嗅皮层(EC)、齿状回(DG)和海马 CA1 区进行了研究。通过免疫组织化学使用胶质纤维酸性蛋白(GFAP)、谷氨酰胺合成酶(GS)和 s100β 染色来可视化星形胶质细胞的形态;使用共聚焦或明场显微镜对这些形态进行成像,以便进行后续的形态计量学分析。与 3 个月龄的小鼠相比,海马 DG 和 CA1 中 GFAP 阳性的星形胶质细胞表现出与年龄相关的进行性肥大,表现为表面、体积和体细胞体积增加。与海马区域相反,衰老诱导 EC 中 GFAP 阳性星形胶质细胞数量减少:与 3 个月龄组相比,24 个月龄的星形胶质细胞的表面、体积和细胞体体积明显减少。与 3 个月龄的动物相比,24 个月龄的海马体两个区域中 GS 阳性星形胶质细胞的细胞表面积较小,而老年小鼠 EC 中的 GS 阳性形态保持不变。s100β 免疫反应性形态的形态计量学显示 EC 显著增加,DG 中度增加,CA1 区无变化。基于 3 种星形胶质细胞标志物的形态分析,我们得出结论,星形胶质细胞以特定于脑区的方式经历复杂的与年龄相关的重塑。

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