Aquaporin-4 expression contributes to decreases in brain water content during mouse postnatal development

The water channel protein aquaporin-4 (AQP4) is implicated to facilitate water efflux from the brain parenchyma into the blood and CSF, playing a critical role in maintaining brain water homeostasis. Nevertheless, its contribution to decreases in brain water content during postnatal development remains unknown. A quantitative Western blot analysis was performed to investigate developmental expression of AQP4 in the whole mouse brain and showed that AQP4 expression level in 1 week-old brain was only 21.3% of that in the adult brain, but significantly increased to 67.4% of the adult level by 2 weeks after birth. Statistical analysis demonstrated that increased AQP4 expression partially relates to decreased brain water content in postnatal mice (r(2)=0.92 and P=0.002). Moreover, AQP4 null mice had greater brain water content than littermate controls from 2 weeks up to adult age. Consistently, mature pattern of AQP4 localization at the brain-blood and brain-CSF interfaces were completed at approximately at 2 weeks after birth. In addition, AQP4 expression in the brain stem and hypothalamus was earlier than that in the cerebral cortex and cerebellum, suggesting a brain regional variation in developmental expression of AQP4. These results characterize the developmental feature of AQP4 expression in the postnatal brain and provide direct evidence for a role of AQP4 in postnatal brain water uptake.