Ho Horace T B, Dahlin Amber, Wang Joanne
Department of Pharmaceutics, University of Washington Seattle, WA, USA.
Front Pharmacol. 2012 Aug 24;3:154. doi: 10.3389/fphar.2012.00154. eCollection 2012.
The choroid plexus (CP) is a highly vascularized tissue in the brain ventricles and acts as the blood-cerebrospinal fluid (CSF) barrier (BCSFB). A main function of the CP is to secrete CSF, which is accomplished by active transport of small ions and water from the blood side to the CSF side. The CP also supplies the brain with certain nutrients, hormones, and metal ions, while removing metabolites and xenobiotics from the CSF. Numerous membrane transporters are expressed in the CP in order to facilitate the solute exchange between the blood and the CSF. The solute carrier (SLC) superfamily represents a major class of transporters in the CP that constitutes the molecular mechanisms for CP function. Recently, we systematically and quantitatively examined Slc gene expression in 20 anatomically comprehensive brain areas in the adult mouse brain using high-quality in situ hybridization data generated by the Allen Brain Atlas. Here we focus our analysis on Slc gene expression at the BCSFB using previously obtained data. Of the 252 Slc genes present in the mouse brain, 202 Slc genes were found at detectable levels in the CP. Unsupervised hierarchical cluster analysis showed that the CP Slc gene expression pattern is substantially different from the other 19 analyzed brain regions. The majority of the Slc genes in the CP are expressed at low to moderate levels, whereas 28 Slc genes are present in the CP at the highest levels. These highly expressed Slc genes encode transporters involved in CSF secretion, energy production, and transport of nutrients, hormones, neurotransmitters, sulfate, and metal ions. In this review, the functional characteristics and potential importance of these Slc transporters in the CP are discussed, with particular emphasis on their localization and physiological functions at the BCSFB.
脉络丛(CP)是脑室中高度血管化的组织,充当血脑脊髓液(CSF)屏障(BCSFB)。脉络丛的主要功能是分泌脑脊液,这是通过小离子和水从血液侧到脑脊液侧的主动转运来实现的。脉络丛还为大脑提供某些营养物质、激素和金属离子,同时从脑脊液中清除代谢物和外源性物质。脉络丛中表达了许多膜转运蛋白,以促进血液和脑脊液之间的溶质交换。溶质载体(SLC)超家族是脉络丛中主要的转运蛋白类别,构成了脉络丛功能的分子机制。最近,我们利用艾伦脑图谱生成的高质量原位杂交数据,系统地、定量地检测了成年小鼠大脑20个解剖结构全面的脑区中Slc基因的表达。在这里,我们使用先前获得的数据,将分析重点放在BCSFB处的Slc基因表达上。在小鼠大脑中存在的252个Slc基因中,有202个Slc基因在脉络丛中以可检测水平被发现。无监督层次聚类分析表明,脉络丛Slc基因表达模式与其他19个分析的脑区有很大不同。脉络丛中的大多数Slc基因以低到中等水平表达,而有28个Slc基因在脉络丛中表达水平最高。这些高表达的Slc基因编码参与脑脊液分泌、能量产生以及营养物质、激素、神经递质、硫酸盐和金属离子转运的转运蛋白。在这篇综述中,讨论了这些Slc转运蛋白在脉络丛中的功能特性和潜在重要性,特别强调了它们在BCSFB处的定位和生理功能。