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Abstract: PO1105

The Enhanced Expression of AQP4 in Cerebral Ischemia Is Attenuated in AQP11 Heterologous Knockout Mice

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Tanaka, Yasuko, Meiji Yakka Daigaku, Kiyose, Tokyo, Japan
  • Ishibashi, Kenichi, Meiji Yakka Daigaku, Kiyose, Tokyo, Japan
Background

The role of aquaporins (AQPs) in the brain edema needs to be clarified to advance its treatment. Since the importance of AQP4 for the formation of brain edema has been shown, AQP11, expressed in the brain capillary, may also be important for the regulation of brain edema. In fact, we recently reported the associated expression of AQP4 and AQP11 in osmotically challenged AQP11 heterologous knockout mice (HKM) (Koike S et al. Biochimie. 2021).

Methods

Both common cervical arteries were ligated for 15 min or 60 min to produce an ischemic-reperfusion model of brain infarction. On one or two days after the reperfusion, total RNA in the brain between Bregma and Lambda was isolated from wild mice and HKM. A real-time RT-qPCR was employed to examine the expression levels of several genes including AQP1, AQP4, AQP11, Iba1 (microglial marker), GFAP (astrocyte marker), Lamp2 (pro-autophagic factor), Bax (pro-apoptotic factor).

Results

Gene expression profiles were similar between wild mice and HKM in Iba1 (increase), Lamp2 (increase) with more severity in 60 min ligation and in the second day. A similar profile was also observed with slightly decreased AQP1 by 5-22%. In contrast, the expression profiles of AQP4 and GFAP were outstanding in that both were more highly induced in wild mice than HKM, by 56% vs. 21% and by 570% vs. 335%, respectively, with further increases in 60 min ligation and in the second day. The results suggested the activation of astrocytes expressing AQP4 by the reperfusion, which might be attenuated in HKM. In agreement with this, the expression of Bax was increased in wild mice by 18% with 60-min ligation while it was decreased by 12% in HKM, suggesting a smaller brain damage in HKM. Interestingly, AQP11 expression was decreased after reperfusion by 13-25% in wild mice while it was decreased more in HKM by 25-30%. The results suggest that this further AQP11 decrease in HKM may have attenuated the increasing AQP4 expression after reperfusion.

Conclusion

The decreased AQP11 expression in HKM attenuated the enhanced expression of AQP4 and Bax in a mouse ischemia-reperfusion brain model. Thus, the inhibition of AQP11 may alleviate the brain edema by attenuating the expression of detrimental AQP4 in brain infarction.

Funding

  • Government Support – Non-U.S.