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Parkinson's Disease and Related Disorders

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

パーキンソン病患者iPS 細胞由来神経細胞におけるドパミン受容体の発現変化の解析
Changes in dopamine receptor expression in iPSC-derived neurons of patients with familial Parkinson’s disease

  • P2-301
  • 葛巻 直子 / Naoko Kuzumaki:1,2 須田 雪明 / Yukari Suda:1 成田 道子 / Michiko Narita:1 岩澤 千鶴 / Chizuru Iwasawa:1 松尾 美里 / Miri Matsuo:1 赤松 和土 / Wado Akamatsu:2,3 服部 信孝 / Nobutaka Hattori:4 岡野 栄之 / Hideyuki Okano:2 成田 年 / Minoru Narita:1,5 
  • 1:星薬科大学  / Hoshi Univ. Sch. Pharm. Pharmaceut. Sci., Tokyo, Japan 2:慶應義塾大学 医学部 生理学教室 / Dept. Physiol., Keio Univ. Sch. Med. Tokyo, Japan 3:順天堂大学大学院医学研究科ゲノム・再生医療センター / Juntendo Univ. Grad. Sch. Med., Tokyo, Japan 4:順天堂大学 医学部 脳神経内科 / Dept. Neurol., Juntendo Univ. Grad. Sch. Med., Tokyo, Japan 5:先端生命科学研究センター (L-StaR) / Life Science Tokyo advanced Recerch Center (L-StaR), Tokyo, Japan 

iPS cells are pluripotent cells which give rise to all cells in the organism. It is well-known that dopamine is a key modulator in the brain control, motor function, emotional states and endocrine physiology. Furthermore, it has been reported that dopamine receptor agonists regulate cell cycle and proliferation. In the present study, we evaluated the change in the dopaminergic system of familial Parkinson's disease- specific "induced pluripotent stem cell" (iPSCs)-derived neurons. Here we profiled the expression of dopamine-related genes in undifferentiated human iPS cells and differentiated neural stem cells. Dopamine D1 and D2 receptors were expressed along with the progress of cell differentiation. Interestingly, D3 receptor expression was gradually decreased with the progress of cell differentiation. Furthermore, we generated the Parkinson disease-specific iPSCs and investigated the possible change in dopamine receptor expression. Expression of dopamine D1 receptor was dramatically decreased in Parkinson's disease specific-iPSCs-derived dopaminergic neurons, whereas dopamine D2 receptor was significantly increased in Parkinson's disease specific-iPSCs-derived dopaminergic neurons. Under these conditions, there were no differences in the potency of differentiation into dopaminergic neurons between control and Parkinson's disease. These findings suggest that the changes in the expression of dopamine receptors in Parkinson's disease specific-iPSCs-derived dopaminergic-neurons could affect neural dysfunction and degeneration.

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