Deciphering molecular interactions of AQP4 at the gliovascular interface in brain

Astrocytes can functionally be defined as the true caretaker cells of the brain that provide for cellular and organ homeostasis. Key elements in achieving this function are the specialised endfeet of astrocytes that ensheath the entire brain vasculature and contain an abundance of the water channel aquaporin-4 (AQP4). Endfoot levels of this protein are perturbed in several brain diseases. This has functional significance and justifies why it is important to understand how AQP4 is regulated. In his doctoral thesis, Hoddevik has studied AQP4 in an animal model of epilepsy and systematically examined intra- and extracellular factors that may regulate AQP4 levels in endfeet. Evidence is provided in support of the hypothesis that pericytes, endothelial cells, the extracellular matrix proteins agrin and laminin as well as the intracellular anchoring protein α-syntrophin all play such a role. The studies also unravelled significant variations of the endfeet and basal lamina composition of these proteins within the brain. Such regional heterogeneity may be of relevance to our understanding of CNS waste clearance, sleep and region-specific disorders such as neuromyelitis optica