Dept of Physiology

  Yokohama City University

   School of Medicine
 

   Fuku-ura 3-9

   kanazawa-ku Yokohama,

   Japan. 236-0004
      TEL 81-45-787-2579
      FAX 81-45-787-2578
 

 




Japanese

Synaptic plasticity and its clinical application

My personal interest is the molecular mechanisms underlying synaptic functions and their clinical application. We have focused on AMPA receptors for over a decade. We discovered experience or learning drives AMPA receptors into synapses. We also found neonatal maltreatment alters synaptic AMPA receptor trafficking. Further, we have developed novel techniques to optically-inactivate AMPA receptors in vivo. While those research have been conducted with rodent using molecular and cellular biological techniques, electrophysiological approach, and imaging with two photon laser scanning microscope, I got interested in the application of findings obtained from basic neuroscience on synapses to human biology to clinics. In collaboration with FUJIFILM, we found a compound which facilitates synaptic AMPA receptor delivery leading to the acceleration of recovery of motor function with rehabilitation after brain injury. We also identified a target protein, and target protein deficient mice failed to exhibit the acceleration of motor function recovery after brain injury with this compound. This prominent effect was also observed in non-human primate. We are currently preparing for the clinical trial of this compound. We also developed a probe to detect AMPA receptors with positron emission tomography (PET). We could observe specific high quality signal in the brain of non-human primate. We performed first-in-human test and detected potential specific binding signals in living human brain. We started imaging patients of various neuronal disorders such as depression, schizophrenia, addiction, epilepsy, stroke and neurodegenerative diseases.