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演題詳細

Poster

不安障害
Anxiety Disorders

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

抗うつ様行動を示すHDAC6ノックアウトマウスの脳セロトニン神経細胞におけるエネルギー代謝異常
Energy dysfunctions in serotonergic neurons in HDAC6 knockout mouse

  • P2-340
  • 川口 禎晴 / Yoshiharu Kawaguchi:1 深田 斉秀 / Masahide Fukada:1 竹島 京子 / Kyoko Takeshima:1 中山 敦雄 / Atsuo Nakayama:1 
  • 1:愛知県心身障害者コロニー発達障害研究所 / Inst. for Dev. Res., Aichi Human Service Ctr. 

Energy dysfunctions in serotonergic neurons in HDAC6 knockout mouse

Yoshiharu Kawaguchi, Masahide Fukada, Kyoko Takeshima, and Atsuo Nakayama

Department of Embryology, Institutes for Developmental Research, Aichi Human Service Center

Abstract:
HDAC6, a cytoplasmic deacetylase, targets alpha-tubulin, and Hsp90, cortactin, and associates with multiple cytoplasmic events. We have demonstrated that Hdac6 is strongly expressed in serotonergic neurons in Median and Dorsal Raphe, and that loss of its deacetylase activity causes antidepressant-like behavior in mouse. To study the underlining mechanism, we focused to the features of serotonergic neurons in Hdac6 KO mice, and found the accumulation of pyruvate in Raphe. This aberrant accumulation was recapitulated in TSA-treated and Hdac6 knock-down neuronal cells, suggesting the possibility of impairment of enzymatic activity in pyruvate dehydrogenase complex (PDC). To examine this, we evaluated the amount of PDC-E1 and E2, components of PDC, and also complex formation in Raphe. However, protein levels and binding of PDC-E1 and E2 were normal compared with WT mice. These findings demonstrate that loss of HDAC6 activity causes energy dysfunction in Raphe, and that PCD itself might not be involved in accumulation of pyruvate in serotonergic neurons.

This work is supported by KAKENHI 24500453 (YK)

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