2017 Fiscal Year Annual Research Report
Therapeutic potential of the metabolic relationship between the product of two genetic markers for pain (gch1 and mthfr)
| Project/Area Number |
15K10556
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
J・P Bellier 滋賀医科大学, 神経難病研究センター, 助教 (80346022)
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| Co-Investigator(Kenkyū-buntansha) |
林 維光 滋賀医科大学, 医学部, 助教 (80242973)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | Tetrahydropbiopterin / Serotonin / GTP Cyclohydrolase 1 / pain / immunotherapy |
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| Outline of Annual Research Achievements |
GTP Cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the biosynthetic pathway for tetrahydrobiopterin (BH4) and is known as a marker for neuropathic pain. BH4 level may regulate availability in the neurotransmitters involved in the nociception. Therefore BH4 might be a lever to control pain signaling. We have produced a specific monoclonal antibody against the regulated form of GCH1, preferentially localized in the sensory system. We attempted to use this antibody in an immunotherapy strategy in the DRG, while in vitro experiments demonstrated the ability of the antibody to reduce GCH1 activity, in vivo it shows mitigate results, most probably because of the difficulty in delivering the antibody intracellulary in the sensory neurons. In addition, a newly raised polyclonal antiserum against GCH1 has been shown to be useful for delineating the enteric nervous system. This novel antibody shows to be extremely useful for the 3D reconstruction of the enteric nervous system organization using recent whole-mount clarification methods. Applying such method, we were able to observed change in the ENS organization in a rat model of visceral pain. Suggesting that GCH1 may play a role in the control of the visceral pain.
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