Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus.

Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus.
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DOI:
10.1016/j.neuroscience.2011.01.020
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发表时间:
2011-03-31
期刊:
影响因子:
3.3
通讯作者:
Binder DK
Binder DK
中科院分区:
医学3区
文献类型:
--
作者:
Hsu MS;Seldin M;Lee DJ;Seifert G;Steinhäuser C;Binder DK

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水通道AQP 4缺陷的小鼠表现出对海马刺激的响应增加的癫痫发作持续时间以及受损的细胞外K+清除。然而,AQP 4在海马中的表达并没有得到很好的描述。在这项研究中,我们调查i)AQP 4在海马中表达的发育,层状和细胞类型特异性; ii)Kir4.1缺失对AQP 4表达的影响; iii)进行Western blot和RT-PCR分析。WT或Kir4.1-/-小鼠冠状切片上的AQP 4免疫组织化学显示发育调节和层特异性模式,在CA 1层腔隙分子层(SLM)和齿状回(DG)的分子层(ML)中表达最高。AQP 4与胶质细胞标记物GFAP和S100 β在海马中共定位,并且在血管周围的星形胶质细胞终足上也普遍表达。在Kir4.1-/-小鼠中没有观察到AQP 4免疫反应性的差异。单个细胞的电生理和记录后的RT-PCR分析显示,AQP 4和Kir4.1共表达在几乎所有的CA 1星形胶质细胞。在NG 2细胞中,AQP 4也在转录水平上表达。这项研究是第一次检查次区域AQP 4表达在海马发育过程中。AQP 4在CA 1 SLM和DG ML中的显著高表达将这些区域确定为星形胶质细胞K+和H2O调节的潜在位点。这些结果开始描绘海马亚区和细胞类型的K+和H2O稳态的功能能力,这是至关重要的兴奋性,并作为一个潜在的目标调制在不同的疾病。
Mice deficient in the water channel AQP4 demonstrate increased seizure duration in response to hippocampal stimulation as well as impaired extracellular K+ clearance. However, the expression of AQP4 in the hippocampus is not well described. In this study, we investigated i) the developmental, laminar and cell-type specificity of AQP4 expression in the hippocampus; ii) the effect of Kir4.1 deletion on AQP4 expression; and iii) performed Western blot and RT-PCR analyses. AQP4 immunohistochemistry on coronal sections from WT or Kir4.1-/- mice revealed a developmentally-regulated and laminar-specific pattern, with highest expression in the CA1 stratum lacunosummoleculare (SLM) and the molecular layer (ML) of the dentate gyrus (DG). AQP4 was colocalized with the glial markers GFAP and S100ß in the hippocampus, and was also ubiquitously expressed on astrocytic endfeet around blood vessels. No difference in AQP4 immunoreactivity was observed in Kir4.1-/- mice. Electrophysiological and postrecording RT-PCR analyses of individual cells revealed that AQP4 and Kir4.1 were co-expressed in nearly all CA1 astrocytes. In NG2 cells, AQP4 was also expressed at the transcript level. This study is the first to examine subregional AQP4 expression during development of the hippocampus. The strikingly high expression of AQP4 in the CA1 SLM and DG ML identifies these regions as potential sites of astrocytic K+ and H2O regulation. These results begin to delineate the functional capabilities of hippocampal subregions and cell types for K+ and H2O homeostasis, which is critical to excitability and serves as a potential target for modulation in diverse diseases.
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期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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