Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4

Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4
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DOI:
10.1007/s11357-011-9330-5
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发表时间:
2013-02-01
期刊:
AGE
影响因子:
--
通讯作者:
Kanungo, Madhusudan
Kanungo, Madhusudan
中科院分区:
医学2区
文献类型:
--
作者:
Gupta, Rajaneesh Kumar;Kanungo, Madhusudan

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神经胶质细胞,除了作为被动的支持基质参与,还提出参与通过严格控制离子和水的稳态的突触传递的间隙空间的优化。在成年小鼠脑中,内向整流K+(Kir4.1)和水通道蛋白-4(AQP 4)通道定位于与脑微血管和谷氨酸突触接触的星形胶质细胞终足,优化细胞外K+和水从突触层的清除。然而,Kir4.1和AQP 4通道的表达是否存在年龄依赖性差异,特别是在出生后发育和衰老过程中,当大脑发生各种显著变化时,这些变化是否具有区域特异性,目前尚不清楚。采用RT-PCR和免疫印迹技术比较了Kir4.1和AQP 4 mRNA和蛋白在出生后0、15、45天、成年(20周)和老年(70周)小鼠大脑和小脑皮质中的相对表达。Kir4.1和AQP 4 mRNA和蛋白表达在0天时非常低。一个显着的和连续的增长,观察到成熟的出生后年龄(15-,45天)。然而,在70周龄小鼠中,与20周龄小鼠相比,表达显著上调。这两种基因在大脑和小脑皮质中遵循相同的年龄相关模式。Kir4.1和AQP 4通道在出生后早期和衰老过程中可能在脑K+和水平衡中发挥重要作用。
Glial cells, besides participating as passive supporting matrix, are also proposed to be involved in the optimization of the interstitial space for synaptic transmission by tight control of ionic and water homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize to astroglial endfeets in contact with brain microvessels and glutamate synapses, optimizing clearance of extracellular K+ and water from the synaptic layers. However, it is still unclear whether there is an age-dependent difference in the expressions of Kir4.1 and AQP4 channels specifically during postnatal development and aging when various marked changes occur in brain and if these changes region specific. RT-PCR and immunoblotting was conducted to compare the relative expression of Kir4.1 and AQP4 mRNA and protein in the early and mature postnatal (0-, 15-, 45-day), adult (20-week), and old age (70-week) mice cerebral and cerebellar cortices. Expressions of Kir4.1 and AQP4 mRNA and protein are very low at 0-day. A pronounced and continuous increase was observed by mature postnatal ages (15-, 45-days). However, in the 70-week-old mice, expressions are significantly up-regulated as compared to 20-week-old mice. Both genes follow the same age-related pattern in both cerebral and cerebellar cortices. The time course and expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K+ and water homeostasis in early postnatal weeks after birth and during aging.