Aquaporin-1 in the choroid plexuses of developing mammalian brain

Abstract

The normal brain develops within a well-controlled stable internal "milieu" protected by specialised mechanisms referred to collectively as blood-brain barriers. A fundamental feature of this environment is the control of water flow in and out of the developing brain. Because of limited vascularisation of the immature brain, choroid plexuses, via the cerebrospinal fluid, have been proposed as the main route of fluid exchange between the blood and brain interfaces. We describe the temporal expression and appearance of aquaporin-1 (AQP1) which is important for water transfer across adult choroid plexuses. AQP1 expression was studied in rat embryos using real time reverse transcription/polymerase chain reaction. mRNA for AQP1 was present in rat brain at embryonic day 12 (E12) one day before the protein was detectable in the fourth ventricular choroid plexus (the first plexus to appear); its relative levels increased at E13-E14 when more AQP1-immunoreactive cells appeared in all plexuses. The presence of AQP1 was determined immunocytochemically in five different mammalian species (rat, mouse, human, sheep and opossum) in all four choroid plexuses from their earliest appearance. In all five species studied, the appearance of AQP1 immunoreactivity followed the same developmental sequence: the fourth, lateral and, finally, third ventricular choroid plexus. The stage of choroid plexus development when AQP1 was first detected in all five species and in all four choroid plexuses corresponded to the transition between Stages I and II. The cellular localisation of AQP1 in all choroid plexuses, as soon as it was detectable, had the characteristic apical membrane distribution previously described in the adult; a basolateral membrane localisation was also observed.

Brain endothelial cells and the glio-vascular complex

“…AQP9 mediates transport not only of water, but also of monocarboxylates, glycerol, purines, pyrimidines, and other solutes (Badaut and Regli 2004;Warth et al 2007). AQP1 is known as the main water channel of the epithelial cells of the choroid plexus (Speake et al 2003;Johansson et al 2005) but is also present in endothelial cells. In cell culture of microvessel endothelial cells from rat brain, AQP1 expression is up-regulated during passages, but down-regulated if cocultured with astrocytes (Dolman et al 2005).…”

The transcription factor Otx2 regulates choroid plexus development and function

“…The ChPs are formed between embryonic day (E) 11 and 14 in the mouse, with the fourth ventricular (hindbrain) ChP differentiating first followed by the two lateral ventricular and later the third ventricular ChP (Dziegielewska et al, 2001). The ChPs acquire barrier, secretory and transport capacities shortly after formation (Møllgård et al, 1976;Ek et al, 2003;Johansson et al, 2005;Johansson et al, 2006;Liddelow et al, 2009;Ek et al, 2010). This early functionality and their localization inside the cerebral ventricles, together with their appearance during the period of neurogenesis, make them uniquely suited for influencing CSF composition and thereby regulating development of the neural stem cells that are in contact with the ventricle along the entire neuraxis (e.g.…”

Low levels of Na, K-ATPase and carbonic anhydrase II during choroid plexus development suggest limited involvement in early CSF secretion

“…More recent evidence suggests that fluid secretion starts much earlier in development, as soon as the choroid plexuses appear. In the rat the lateral ventricular choroid plexus first appears around E14 [8,13] and the aquaporin-1 water channel is present in the choroid plexus epithelial cells, in an adult-like pattern, from E15 [13]. The presence of AQP1 at E15 strongly suggests CSF formation at this age.…”

“…During this period the cerebral ventricles more than double in size [12] and AQP1 water channels are already present in an adult-like pattern [13] implying secretion of fluid. The low levels of NKA and CAII during this period suggest that alternative mechanisms are likely to be involved.…”