A brief report on the JSPS Invitation Award for Eminent Scientist
- Professor Peter Agre in Niigata University, 2005 -

1. Invited Eminent Researcher
   Peter Agre
   Professor, Departments of Biological Chemistry and Medicine
   School of Medicine, Johns Hopkins University
   
   
2. Host
   Tsutomu Nakada
   Professor and chairman, Center for Integrated Human Brain Science,
   Brain Research Institute, Niigata University
   
   
3. Duration of Invitation
   January 10, 2005 to January 16, 2005
   
   
4. Schedule of the Stay
   January 10, 2005 (Departure from USA)
   11:15 Departed from Washington Dulles International Airport (NH001)
   January 11, 2005 (Arrival in Japan)
   15:25 Arrived at Tokyo Narita Airport
   January 12, 2005 (Niigata)
   Arrived Center for Integrated Human Brain Science, Brain Research Institute, Niigata University
   Participated Scientific Meeting of Brain Research Institute
   January 13-15, 2005 (Niigata)
   Inspected the satellite laboratory in Center for Integrated Human Brain Science, Brain Research Institute, Niigata University
   January 16, 2005 (Departure from Japan and arrival in USA)
   11:10 Departed from Tokyo Narita Airport (NH002)
   09:40 Arrived at Washington Dulles International Airport
5. Summary
   Since Prof. Agre has been committed with many lectures around the world, the duration of his visit in this fiscal year was limited to 6 days, and he only stayed in Niigata. Nevertheless, he intensively interacted with many researches in the Center for Integrated Human Brain Science at Niigata University. He influenced them by taking about his discovery of aquaporin, and encouraged them for their future researches by individual conversation sincerely. He was also very impressed with the highest level of technology at the Center, including 7T MRI equipped recently. We initiated our mutual scientific collaboration on the project entitled "Roles of aquaporins in human brain function." We therefore believe that his visit was very productive, and that we could expand our collaboration on aquaporin research further.
6. Educative Activities within the University
   Importance of discovery
   Prof. Agre initiated his interaction with the researchers at the Center by talking about his discovery of aquaporin, water channel. “By sheer blind luck we sort product of our experiments to isolate the Rh, or rhesus, factor in red blood cells. The abundance of this "contaminant" got us interested in what it might be. It turned out to be a protein that forms pores in cell membranes and selectively conducts water molecules through, while preventing the passage of ions and other small molecules, and so on.” We were inspired the importance of discovery and encouraged to challenge.
   
   Clinical implication of AQP
   Prof. Agre also emphasized on clinical implication of the basic research. He said, "We are now learning that a wide range of clinical conditions- including brain edema, cirrhosis, congestive heart failure, and glaucoma- are linked to compromised aquaporin function, and in some cases, they are devising potential therapies based on their findings. Despite the fact that aquaporin research has great clinical relevance, it may take time before any health benefits are realized." We were convinced that many investigations are still necessary on aquaporin research to the goal.
   
   
7. Collaborative Researches
   Aquaporin-4 (AQP4), cloned and characterized by Prof. Agre's group, is the predominant aquaporin in mammalian brain. AQP4 is strongly expressed in astrocytes membranes that are in direct contact with capillaries, and pia, consistent with a role for mediators of water metabolism in brain. In the pathological conditions, AQP4 is involved in the development of post-ischemic brain edema. Thus, AQP4 can be the target molecule to develop new therapeutic drugs for preventing brain edema. However, physiological relevance of AQP4 is still largely unknown. There is accumulating evidence suggesting that water permeability of the astrocyte membrane may be dynamically regulated through AQP4.
   Prof. Nakada at the Center for Integrated Human Brain Science has been interested in understanding how the human brain functions. He has developed high-field MRI system for use in functional imaging, and developed the first vertical MRI. Prof. Nakada has contributed to understanding the functional organization of the cerebral cortex in processes such as language, music recognition, stereoscopic perception, and sensorimotor processing using these imaging systems and 256-channel electroencephalography recording systems. He has recently proposed a new theory to explain the basis of cognition and consciousness, with a central role for astrocytes and astrocyte-mediated water homeostasis.
   The aim of this collaborative project is therefore to understand the role of AQP4 in the human brain functions under physiological and pathological conditions. The collaborative research entitled on "Roles of aquaporins in human brain function" was initiated by discussing the following specific aims:
   
   

   Aim 1:	Generation and phenotypic analyses of aquaporin-4 (AQP4) conditional knockout mice.
   Aim 2:	Immunohistological analyses of human AQP4 under several pathological conditions.
   Aim 3:	Identification of human brain diseases related to AQP4 and its associated proteins.
   Aim 4:	Application of 7T MRI and fMRI to human AQP4 research.

   
   
8. Future Perspective
   Prof. Agre’s satellite lab in the Center
   Prof. Agre and Prof. Nakada have discussed about the possibility that Agre’s satellite laboratory will be established in the Center to facilitate the active collaboration, including exchanging the researchers.
   
   Aquaporin Symposium in Japan:
   Prof. Agre and Prof. Nakada have discussed to organize the mini-symposium about aquaporins in brain functions. They think that the symposium should be open to other institutions.

   We hear that Prof. Agre’s schedule will be more flexible in the next fiscal year. We hope that his next visit will be longer and stimulate aquaporin researches further not only in the Center at Niigata but also in other Japanese institutions.