Aquaporin-4 maintains ependymal integrity in adult mice

Ependymal cells form the walls of the ventricles, and take part in the production of cerebrospinal fluid (CSF). Aquaporin-4 (AQP4), a predominant water channel of the brain, is restricted to basolateral plasma membranes of ependymal cells. The highly polarized expression of AQP4 suggests it may be involved in maintaining the structural and functional integrity of the ependyma. This hypothesis was validated by using adult AQP4 knockout mice generated by our laboratory [Fan Y, Zhang J, Sun XL, Gao L, Zeng XN, Ding JH, Cao C, Niu L, Hu G (2005) Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice. J Neurosci Res 82:458–464]. Histological analysis showed disorganized ependymal layer of the lateral ventricle and aqueduct in AQP4-deficiency mice. A majority (92.7%) of null mice displayed reduced lateral ventricular volume, while a small fraction (7.3%) had enlarged or normal ventricular size with a narrow aqueduct. Immunohistochemistry demonstrated that AQP4 deletion resulted in decreased expression of gap junction protein connexin43 in the ependymal cells. Electron microscopy confirmed junctional complex absence at basolateral membranes of ependymocytes. Moreover, AQP4 knockout mice showed decreased CSF production and increased brain water content compared with wild-type mice. These results highlight a key role of AQP4 in maintaining the structure and function of the ependyma. In addition, variable profiles of ventricle system in adult AQP4 null mice indicate functional AQP4 polymorphisms.