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Staining, Tracing, and Imaging Techniques

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Novel method for development of the new PET probes detecting AMPA receptors

  • P2-388
  • 芹澤 麻美 / Asami Serizawa:1 柴田 裕介 / Yuusuke Shibata:1 黒木 洋子 / Youko Kuroki:1,2 宮崎 智之 / Tomoyuki Miyazaki:1,2 高橋 琢哉 / Takuya Takahashi:1 
  • 1:横浜市立大学大学院 医学研究科 生理学 / Department of Physiology, Yokohama City University School of Medicine 2:横浜市立大学大学院 医学研究科 麻酔科学 / Department of Anesthesiology, Yokohama City University Graduate School of Medicine 

When experiencing or learning, some plastic changes occur in synapses and drive AMPA receptors (AMPA-Rs) into postsynaptic membrane. Moreover, interruption of AMPA-Rs trafficking into synapse disrupts newly learning. These studies establish that AMPA-Rs work as a key molecular machinery underlying experience and learning.
Recent studies using postmortem brains revealed the quantitative alteration of AMPA-Rs may relate to some variety of mental disorders including schizophrenia, depression and ASD. Among these studies, membrane numbers of AMPA-Rs seem to account for these disorders. However, with the current techniques, we cannot observe the behavior of AMPA-Rs in living human brains. Our study aim to develop new PET probes to detect the membrane numbers of AMPA-Rs in living human brains.
We disclosed that animals experiencing inhibitory avoidance (IA) task increase the membrane surface expressions of AMPA-Rs up to 1.5-fold of control animals in the hippocampus. To detect these changes in vivo, we developed new method using LC/MS-MS. Briefly, we administered compounds previously known to bind to AMPA-Rs specifically to adult rats intravenously. 24 hours later, we dissected hippocampus and measure these compounds in the hippocampus using LC/MS-MS. Then we analyze the correlation between biochemical data and MS data.
As a result, some compounds increased in IA+ animals compared to control animals. These results indicate that these compounds detect the increase of surface expression of AMPA-Rs in vivo.

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