Delayed peripheral nerve rehabilitation in aquaporin-3 deficiency in mouse models of sciatic nerve contusion.

Aquaporin-3 (AQP3) water channels are belonging to the aquaporin water channel family, permeable not only to water but also to some small solutes such as glycerol and lactate. The purpose of this study is to investigate the possible functions of AQP3 in peripheral nerve rehabilitation based on AQP3-deficient mice. Mature 8-week-old female AQP3-deficient (AQP3-/-) mice and C57BL/6 (WT) mice initially weighing 25~30 g were used in this study. Schwann cells were isolated from sciatic nerves of WT and AQP3-/- mice respectively. AQP3 mRNA and protein expression in sciatic nerve tissues and Schwann cells were detected by RT-PCR, immunoblot analysis, and immunofluorescence staining. Sciatic nerve cross sections from the WT and AQP3-/- mice were stained by toluidine-blue agent to identify the potential influence of AQP3 deficiency to the morphology nerve fibers. The proliferation and migration ability of AQP3-/- and WT Schwann cells were observed in primary cell cultures. To explore the possible role of AQP3 in nerve repair processes, sciatic nerve contusion models were established and walking track analysis was performed on both WT and AQP3-/- mice. AQP3 was localized in the membrane of Schwann cells. AQP3-deficiency did not alter the morphology of fibers in the sciatic nerve. There was an increase of AQP3 protein expression in the sciatic nerve of wild-type mice after injury. Primary culture of Schwann cells and in vitro wound healing model revealed that AQP3-deficient Schwann cells exhibited the same morphology, while showing lower proliferation and migration ability compared with wild-type Schwann cells. There was obvious delay in motor function rehabilitation in AQP3-deficient mice compared with that of wild-type mice. Our study suggested that AQP3 localized in the membrane of Schwann cells and facilitated Schwann cells' proliferation and migration. AQP3 deficiency impaired nerve rehabilitation in wound healing model both in vitro and in vivo. The study support our hypothesis that AQP3 participates in myelin damnification and repair course and the mechanisms underlying the AQP3 in the field of myelin repair and regeneration in peripheral nerves deserves further investigation and exploration in detail.