Aquaporins and The Nervous System: from Bench to Bedside

Water is the single most abundant substance in cells and organisms and is an important molecule involved in several biochemical processes present in living cells. In humans 60-70% of body weight is water which equilibrates across the lipid bilayer in cell membranes. Forty years ago, a small number of scientists argued that specialized water-selective pores are necessary to explain the high water permeability of red blood cells and renal tubules. Therefore, the molecular identification of a 28 kDa integral membrane protein in these cells has characterized a new stream of research. Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol and urea. Each subtype has its own cellular distribution and distinct regulatory mechanisms of their expression. Their classical role in facilitating transepithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion, while the molecular mechanisms to regulate water permeability in the nervous system are still unclear. Maintenance of the ionic and osmotic composition and volume of interstitial, glial and neuronal compartments within the nervous system is essential for normal function. Small changes in intracellular or extracellular ion or solute composition can dramatically modify bi-directional water pathway between the brain and blood vessels and alter cerebrospinal fluid formation, neural signal transduction and information processing. To date, only some AQP isoforms (AQP1, 3, 4, 5, 8, 9) have been reported in the central nervous system being identified in choroidal cells (AQP1), astrocytes (AQP1, 3, 4, 5, 8, 9), oligodendrocytes (AQP8), neurons (AQP1, 5, 8), tanycytes (AQP9) and ependymal cells (AQP1, 4, 9). In contrast to numerous studies of AQP localization and function in the central nervous system, little information is available on the expression and function of AQPs in peripheral nervous system. This issue includes six review articles in which the authors report and explore the recent findings about the involvement of AQPs both in peripheral and central nervous system.