Boassa Daniela, Yool Andrea J
Department of Physiology, University of Arizona College of Medicine, Tucson, Arizona 85724, USA.
Curr Top Dev Biol. 2005;67:181-206. doi: 10.1016/S0070-2153(05)67005-6.
The choroid plexus is a specialized tissue that lines subdomains within the four ventricles of the brain where most of the cerebrospinal fluid is produced. Maintenance of an equilibrium in volume and composition of the cerebrospinal fluid (CSF) is vital for a normal brain function, ensuring an optimal environment for the neurons. The necessarily high water permeability of the choroid plexus barrier is made possible by the abundant expression of a water channel, Aquaporin-1 (AQP1), on the apical side of the membrane from early stages of development through adulthood. Data from studies of AQP1 suggest that it also can contribute as a gated ion channel, and suggest that the AQP1-mediated ionic conductance has physiological significance for the regulation of cerebrospinal fluid secretion. The regulation of AQP1 ion channels could be one of several transport mechanisms that contribute to the decreased CSF secretion in response to endogenous signaling molecules such as atrial natriuretic peptide. Numerous classes of ion channels and transporters are targeted specifically to each side of the cellular membrane, and they all work in concert to secrete CSF. Several signaling cascades have a direct effect on transporters and ion channels present in the choroid plexus epithelium, altering their transport activity and therefore modulating the net transcellular movement of solutes and water. Several neurotransmitters, neuropeptides, and growth factors can influence CSF secretion by direct effect on transport mechanisms of the epithelium. The mammalian choroid plexus receives innervation from noradrenergic sympathetic fibers, cholinergic and peptidergic fibers that modulate CSF secretion. Water imbalance in the brain can have life-threatening consequences resulting from altered excitability and neurodegeneration, disruption of the supply of nutrients, loss of signaling molecules, and the accumulation of unwanted toxins and metabolites. Understanding the mechanisms involved in the modulation of CSF secretion is of fundamental importance. An appreciation of AQP1 as an ion channel in addition to its role as a water channel should offer new targets for therapeutic strategies in diseases involving water imbalance in the brain.
脉络丛是一种特殊组织，衬于脑的四个脑室的特定区域内，大部分脑脊液在此产生。维持脑脊液（CSF）体积和成分的平衡对于正常脑功能至关重要，可确保为神经元提供最佳环境。从发育早期到成年，脉络丛屏障极高的水通透性是由水通道水通道蛋白-1（AQP1）在膜顶端的大量表达实现的。对AQP1的研究数据表明，它也可作为门控离子通道发挥作用，且AQP1介导的离子传导对脑脊液分泌的调节具有生理意义。AQP1离子通道的调节可能是导致脑脊液分泌减少以响应诸如心房利钠肽等内源性信号分子的几种转运机制之一。众多类型的离子通道和转运体特异性地靶向细胞膜的每一侧，它们协同作用以分泌脑脊液。几种信号级联反应对脉络丛上皮细胞中存在的转运体和离子通道有直接影响，改变它们的转运活性，从而调节溶质和水的跨细胞净移动。几种神经递质、神经肽和生长因子可通过直接影响上皮细胞的转运机制来影响脑脊液分泌。哺乳动物的脉络丛接受去甲肾上腺素能交感纤维、胆碱能和肽能纤维的神经支配，这些神经纤维调节脑脊液分泌。脑内的水失衡可能因兴奋性改变和神经退行性变、营养物质供应中断、信号分子丧失以及有害毒素和代谢产物的积累而产生危及生命的后果。了解参与脑脊液分泌调节的机制至关重要。认识到AQP1除了作为水通道的作用外还可作为离子通道，应为涉及脑内水失衡的疾病的治疗策略提供新的靶点。
