Appears to Be a Key Gene for Sporadic Obstructive Hydrocephalus in the Absence of AQP4.

Abstract

Aquaporin-4 (AQP4) is expressed in ependymal cells bordering the ventricles, the glia limitans, and pericapillary astrocyte endfeet forming the blood-brain barrier. The sporadic occurrence of obstructive congenital hydrocephalus (OH) has been observed in the offspring of AQP4/mice generated in the CD1 strain background. Here, we used microarray analysis to explore gene expression profiles in the periaqueductal area from littermate AQP4/pups at postnatal day 12. We compared wild-type (WT) animals with AQP4/animals that developed OH (AQP4/-OH) and those that did not (AQP4/-NH). Bioinformatic analysis identified gene sets associated with proliferation and migration of microglia, ependymal cell adhesion, extracellular matrix components, axon myelination, and neuronal synapsis. Among the differentially expressed genes,-expressed by neonatal CD11cmicroglia-was highlighted in the triple comparison.was significantly upregulated in AQP4/-NH and downregulated in AQP4/-OH mice. These findings suggest that CD11cmicroglia, viaexpression, play a key morphogenic role in the aqueduct of Sylvius and their absence, occurring in a small subset of AQP4/-CD1 animals, leads to obstructive hydrocephalus.