Mansour Hussein, Chamberlain Coral G, Weible Michael W, Hughes Suzanne, Chu Yi, Chan-Ling Tailoi
School of Medical Sciences (Anatomy and Histology) and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia.
Aging Cell. 2008 Aug;7(4):526-40. doi: 10.1111/j.1474-9726.2008.00402.x. Epub 2008 Jun 28.
The aim of this study was to investigate changes in astrocyte density, morphology, proliferation and apoptosis occurring in the central nervous system during physiological aging. Astrocytes in retinal whole-mount preparations from Wistar rats aged 3 (young adult) to 25 months (aged) were investigated qualitatively and quantitatively following immunofluorohistochemistry. Glial fibrillary acidic protein (GFAP), S100 and Pax2 were used to identify astrocytes, and blood vessels were localized using Griffonia simplicifolia isolectin B4. Cell proliferation was assessed by bromodeoxyuridine incorporation and cell death by TUNEL-labelling and immunolocalization of the apoptosis markers active caspase 3 and endonuclease G. The density and total number of parenchymal astrocytes in the retina increased between 3 and 9 months of age but decreased markedly between 9 and 12 months. Proliferation of astrocytes was detected at 3 months but virtually ceased beyond that age, whereas the proportion of astrocytes that were TUNEL positive and relative expression of active caspase 3 and endonuclease G increased progressively with aging. In addition, in aged retinas astrocytes exhibited gliosis-like morphology and loss of Pax2 reactivity. A small population of Pax2(+)/GFAP(-) cells was detected in both young adult and aged retinas. The reduction in the availability of astrocytes in aged retinas and other aging-related changes reported here may have a significant impact on the ability of astrocytes to maintain homeostasis and support neuronal function in old age.
本研究的目的是调查在生理衰老过程中中枢神经系统中星形胶质细胞密度、形态、增殖和凋亡的变化。对3个月（年轻成年）至25个月（老年）的Wistar大鼠视网膜整装标本中的星形胶质细胞进行免疫荧光组织化学定性和定量研究。使用胶质纤维酸性蛋白（GFAP）、S100和Pax2来识别星形胶质细胞，并使用西非相思豆凝集素B4对血管进行定位。通过溴脱氧尿苷掺入评估细胞增殖，通过TUNEL标记以及凋亡标志物活性半胱天冬酶3和核酸内切酶G的免疫定位评估细胞死亡。视网膜实质星形胶质细胞的密度和总数在3至9个月龄之间增加，但在9至12个月之间显著下降。在3个月时检测到星形胶质细胞增殖，但在该年龄之后几乎停止，而TUNEL阳性的星形胶质细胞比例以及活性半胱天冬酶3和核酸内切酶G的相对表达随衰老而逐渐增加。此外，在老年视网膜中，星形胶质细胞表现出胶质细胞增生样形态且Pax2反应性丧失。在年轻成年和老年视网膜中均检测到一小部分Pax2(+)/GFAP(-)细胞。此处报道的老年视网膜中星形胶质细胞数量减少以及其他与衰老相关的变化可能对星形胶质细胞在老年时维持内环境稳定和支持神经元功能的能力产生重大影响。
