Shifting from ependyma to choroid plexus epithelium and the changing expressions of aquaporin-1 and aquaporin-4

The cells of the choroid plexus (CP) epithelium are specialized ependymal cells (ECs) but have distinct properties. The CP cells and ECs form single-cell sheets contiguous to each other at a transitional zone. The CP is underlined by a basal lamina and has barrier properties, whereas the ECs do not. The basal lamina of the CP is continuous with the glia limitans superficialis and, consequently, the CP stroma is continuous with the meninges along entering blood vessels. The CP has previously been reported to express aquaporin-1 (AQP1) mostly apically, and ECs show mostly basolateral aquaporin-4 (AQP4) expression. Recent evidence in various systems has shown that in changing conditions the expression and distribution of AQP4 can be modified, involving phosphorylation and calmodulin-triggered translocation. Studies on the human CP revealed that AQP4 is also expressed in some CP cells, which is likely to be increased during ageing based on mouse data. Moreover, subependymal astrocytic processes in the ependyma-CP transition, forming a glial plate around blood vessels and facing the CP stroma, were strongly positive for AQP4. We propose that the increased AQP4 expression might be a compensatory mechanism for the observed reduction in CSF production in the ageing human brain. The high AQP4 density in the transition zone might facilitate the transport of water into and out of the CP stroma and serve as a drainage and clearing pathway for metabolites in the CNS.image Abstract figure legend Aquaporin expression in the ependyma, choroid plexus (CP) and the transitional zone in the human brain, depicting changes presumed to occur during ageing. The overview in the centre shows blood vessels entering the CP surrounded by meningeal tissue forming the CP stroma. This tissue is surrounded by a subpial basal lamina continuous with CP epithelial basal lamina. The ependymal lining of the ventricles (green ciliated cells) forms a cell layer that is continuous with the CP epithelial cells. The detailed view on the left shows that in the transition zone this basal lamina is covered by astrocytic processes strongly expressing aquaporin-4 (AQP4), forming a glial plate. Capillaries in the CP stroma are fenestrated, facilitating the secretion of cerebrospinal fluid by CP epithelial cells through transporters and channels, including apical aquaporin-1 (AQP1; detailed view on the right). In the ageing CP, many CP epithelial cells express AQP4 basolaterally. Also, the stroma becomes enlarged by thicker connective tissue, infiltrated immune cells, such as macrophages, and psammoma bodies (concentric spherical structures). It is possible that the AQP4 expression by CP cells compensates for the obstructed diffusion. The capillary fenestration also implies the lack of a barrier between the stroma and the glial plate in the transition zone. We hypothesize that the high density of AQP4 water channels in the glial plate provides a possible clearance pathway for metabolites from the brain parenchyma, draining into stromal blood vessels. The blue arrows indicate suggested water pathways. Created with BioRender.com.image