Suzuki Yuji, Kitaura Hiroki, Nakamura Yukimi, Kakita Akiyoshi, Huber Vincent J, Capozzoli Nicholas, Kwee Ingrid L, Nakada Tsutomu
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan.
Department of Pathology, Brain Research Institute, University of Niigata, Japan.
Heliyon. 2020 Jan 30;6(1):e03259. doi: 10.1016/j.heliyon.2020.e03259. eCollection 2020 Jan.
Aquaporin-4 (AQP4) is a water conducting membrane integral protein channel which is widely expressed in the astrocyte system of the brain. During the development of the AQP4 positron emission tomography (PET) imaging agent [C]TGN-020 (-(1,3,4-thiadiazol-2-yl)pyridine-3-[C]-carboxamide), significant radioligand uptake was observed in the skull, where there was no known distribution of any aquaporin family proteins. Herein we confirmed via a newly developed method for bone-tissue immunohistology, a hitherto unrecognized distribution of AQP4, and not AQP1, in the skull. Other bony structures, by contrast, showed virtually no uptake of [C]TGN-020, and likewise, do not express either AQP4 or AQP1. Immunohistological analysis demonstrated that the AQP4 expression in the skull is restricted to the diploë. Consequently, we suspect AQP4 plays a pivotal role in the formation and maintenance of yellow marrow and the diploë. However, elucidating the exact nature of that role will require further studies.
水通道蛋白4(AQP4)是一种水传导性膜整合蛋白通道,在脑星形胶质细胞系统中广泛表达。在水通道蛋白4正电子发射断层扫描(PET)显像剂[C]TGN - 020(-(1,3,4 - 噻二唑 - 2 - 基)吡啶 - 3 - [C] - 甲酰胺)的研发过程中,在颅骨中观察到显著的放射性配体摄取,而此前并无已知水通道蛋白家族蛋白在颅骨中有分布。在此,我们通过一种新开发的骨组织免疫组织学方法证实,AQP4而非AQP1在颅骨中存在一种此前未被认识到的分布。相比之下,其他骨骼结构几乎未摄取[C]TGN - 020,同样也不表达AQP4或AQP1。免疫组织学分析表明,颅骨中AQP4的表达局限于板障。因此,我们推测AQP4在黄骨髓和板障的形成与维持中起关键作用。然而,要阐明该作用的确切性质还需要进一步研究。