Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan; Corresponding author.
Hiroki Kitaura
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan; Department of Pathology, Brain Research Institute, University of Niigata, Japan
Yukimi Nakamura
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan
Akiyoshi Kakita
Department of Pathology, Brain Research Institute, University of Niigata, Japan
Vincent J. Huber
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan
Nicholas Capozzoli
Neurology Service, VA Northern California Health Care System, USA
Ingrid L. Kwee
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan; Department of Neurology, University of California, Davis, USA
Tsutomu Nakada
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Japan; Department of Neurology, University of California, Davis, USA
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 [11C]TGN-020 (N-(1,3,4-thiadiazol-2-yl)pyridine-3-[11C]-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 [11C]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.
