• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Pain, Itch and Their Disorders

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

Cell-specific Transcriptional Activation of Chemokine Associated with Histone Modifications in Spinal Cord Astrocytes Following Peripheral Nerve Injury

  • P2-180
  • 池上 大悟 / Daigo Ikegami:1,2 大井 香織 / Kaori Ohi:1 成田 道子 / Michiko Narita:1 八重樫 香菜子 / Kanako Yaegashi:1 大塚 まき / Maky Otsuka I.:3 葛巻 直子 / Naoko Kuzumaki:1,4 岡野 栄之 / Hideyuki Okano:3,4 牛島 俊和 / Toshikazu Ushijima:2,3 五十嵐 勝秀 / Katsuhide Igarashi:3 成田 年 / Minoru Narita:1,4 
  • 1:星薬科大学 / Dept. Pharmacol., Hoshi Univ., Sch. of Pharmacy & Pharmceu. Sci., Tokyo, Japan 2:国立がん研究センター研究所・エピゲノム解析分野 / Div. of Epigenomics, National Cancer Center Res. Institute., Tokyo, Japan 3:先端生命科学研究センター (L-StaR) / Life Science Tokyo Advanced research center (L-StaR), Tokyo, Japan 4:慶応義塾大学・医学部・生理学教室 / Dept. Physiol., Keio Univ. Sch. Med., Tokyo, Japan 

Neuropathic pain, which is characterized by spontaneous burning pain, hyperalgesia and allodynia, is most difficult pain to manage in the pain clinic. However, the complicated pathophysiology of neuropathic pain is not yet understood. In the present study, we found that partial sciatic nerve ligation remarkably increased the expression of monocyte chemotactic protein 3 (MCP-3, known as CCL7) in the spinal cord, which lasted for 4 weeks. The robust increases in MCP3 in the dorsal horn of the spinal cord with partial sciatic nerve ligation were seen mostly in astrocytes. Consistent with immunohistochemistry assay, our present magnetic-activated cell sorting assay revealed that the expression of MCP-3 mRNA was significantly increased in GLAST-positive astrocyte cells, but not in myelin-positive oligodendrocyte/neuron population or cd11b-positive microglia population obtained from the spinal cord of mice with nerve ligation. This increase was accompanied by the decreased trimethylation of histone H3 at lysine27 (H3K27me3) at the MCP-3 promoter in GLAST-positive astrocyte cells. In agreement with these data, sciatic nerve ligation significantly increased the induction of Jumonji domein containing 3 (Jmjd3) at MCP-3 promoter in GLAST-positive astrocyte cells. Interestingly, microinjection into the spinal cord with sh-jmjd3 was effective for reversing the neuropathic pain-like behaviors induced by nerve injury. These findings suggest that increased MCP-3 expression associated with epigenetic modification at the MCP-3 promoter after nerve injury, mostly in spinal astrocytes, may serve to facilitate astrocyte-microglia interaction in the spinal cord and could play a critical role in the neuropathic pain-like state.

Copyright © Neuroscience2014. All Right Reserved.