Aquaporin-4 Expression in the Aging Choroid Plexus
Researchers here discuss the rising expression of aquaporin-4 in the vasculature of the aging brain, particularly the choroid plexus, where cerebrospinal fluid is produced. That production decreases with age. Aquaporin-4 is one of a family of proteins that facilitates transfer of water through cell membranes, and it is an important part of the regulation of fluid in the brain. It is unclear as to whether this rising expression is (a) harmful, one of many detrimental alterations that take place in the aging vasculature and brain structures, and a contributing cause of reduced cerebrospinal fluid production, or (b) an ultimately unsuccessful attempt to compensate for some of those harms by increasing cerebrospinal fluid production.
The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells (CPCs) are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP. As previously reported, AQP1 was expressed apically in CPCs. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain.
Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (age 74-91). We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 mRNA in old mice compared to young and adult animals.
In the context of the morphological and functional changes associated with age and disease in the CP, the detection of AQP4 in CPCs and can be interpreted in two alternative scenarios. First, AQP4 expression could serve as a compensatory mechanism in old age to maintain CSF production known to be decreased. An alternative hypothesis can be inferred from AQP4 expression in the ependyma adjacent to the plexus epithelium. Here, AQP4 is expressed in the basolateral membrane domain of ependymal cells. Therefore, CPCs might differentiate over time into AQP4-positive cells, and the expression of AQP4 leads to an inverted transcellular water flow resulting in a reduced CSF production.