Alpha 7 nicotinic acetylcholine receptors availability in schizophrenia: A PET study

• Project/Area Number: 16K10186
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Wakuda Tomoyasu 浜松医科大学, 医学部附属病院, 講師 (80444355)
• Co-Investigator(Kenkyū-buntansha): 横倉 正倫 浜松医科大学, 医学部, 助教 (00529399) ; 間賀田 泰寛 浜松医科大学, 光尖端医学教育研究センター, 教授 (20209399) ; 尾内 康臣 浜松医科大学, 光尖端医学教育研究センター, 教授 (40436978)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ポジトロン断層法 / 統合失調症 / アセチルコリン受容体 / ニコチン性アセチルコリン受容体

Outline of Final Research Achievements

In this study, we aim to clarify availability of α7 nicotinic acetylcholine receptor (α7nAChR) in the brains of patients with schizophrenia using positron emission tomography (PET) with a ligand of [11C](R)-MeQAA. We opted for 4 cortical areas, the middle frontal cortices, superior frontal cortices, hippocampus, and thalamus, as regions of interest (ROIs). There was no significant differences in [11C]MeQAA binding potential(BPND) in patients with schizophrenia compared with healthy controls. However there was a significant negative correlation between the severity of schizophrenia and [11C]MeQAA BPND in the middle frontal cortices, superior frontal cortices, and thalamus. These results indicate that α7 nAChR may be involved in the pathophysiology of schizophrenia, therefore further evaluations with more participants will be required.

Academic Significance and Societal Importance of the Research Achievements

本研究では、PETを用いて統合失調症者のα7nAChRの有用性について検討した。最先端のPET技術を用いて、これまで明らかにされていなかった統合失調症者のα7nAChRの有用性を検討した学術的意義は極めて大きい。また、本研究で統合失調症の症状が重度であるほどα7nAChRの有用性は低い傾向が認められた。今回の成果によりα7nAChRを標的とした統合失調症の新規治療薬の開発につながる可能性がある。

Research Products

• [Journal Article] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect (2019)
  • Author(s): Ikeda M,Takahashi A,Kamatani Y,Momozawa Y,Saito T,Kondo K,Shimasaki A,Kawase K,Sakusabe T,Iwayama Y,Toyota T,Wakuda T,Kikuchi M,Kanahara N,Yamamori H,Yasuda Y,Watanabe Y,Hoya S,Aleksic B,Kushima I,Arai H,Takaki M,Hattori K,Kunugi H,Okahisa Y,Ohnuma T,Ozaki N,Someya T,Hashimoto R,Yoshikawa T,Kubo M,Iwata N
  • Journal Title: Schizophr Bull Volume: 印刷中 Pages: 824-834
  • DOI: 10.1093/schbul/sby140
  • Peer Reviewed / Open Access
• [Journal Article] In vivo depiction of α7 nicotinic receptor loss for cognitive decline in Alzheimer’s disease (2018)
  • Author(s): Nakaizumi K, Ouchi Y, Terada T, Yoshikawa E, Kakimoto A, Isobe T, Bunai T, Yokokura Y, Suzuki K, Magata Y
  • Journal Title: J Alzheimers Dis. Volume: 61 Pages: 1355-1365
  • DOI: 10.3233/jad-170591
  • Peer Reviewed
• [Journal Article] Neuroinflammation following disease modifying therapy in multiple sclerosis A pilot positron emission tomography study (2018)
  • Author(s): Bunai T, Terada T, Kono S, Yokokura M, Yoshikawa E, Futatsubashi M, Miyajima H, Ouchi Y
  • Journal Title: J Neurol Sci. Volume: 385 Pages: 30-33
  • DOI: 10.1016/j.jns.2017.12.004
  • Peer Reviewed
• [Journal Article] Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake. (2018)
  • Author(s): Sugita T, Kondo Y, Ishino S, Mori I, Horiguchi T, Ogawa M, Magata Y.
  • Journal Title: Nucl Med Commun. Volume: 39(8) Pages: 753-760
  • DOI: 10.1097/mnm.0000000000000863
  • Peer Reviewed / Open Access
• [Journal Article] Noninvasive quantitation of rat cerebral blood flow using 99mTc-HMPAO-assessment of input function with dynamic chest planar imaging. (2018)
  • Author(s): Suzuki C, Kosugi M, Magata Y.
  • Journal Title: EJNMMI Res. Volume: 8(1) Pages: 21-21
  • DOI: 10.1186/s13550-018-0375-7
  • Peer Reviewed / Open Access
• [Journal Article] Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia. (2017)
  • Author(s): Balan S, Yamada K, Iwayama Y, Hashimoto T, Toyota T, Shimamoto C, Maekawa M, Takagai S, Wakuda T, Kameno Y, Kurita D, Yamada K, Kikuchi M, Hashimoto T, Kanahara N, Yoshikawa T
  • Journal Title: Schizophr Res. Volume: 印刷中 Pages: 33-40
  • DOI: 10.1016/j.schres.2017.01.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Perinatal Asphyxia in Rat Alters Expression of Novel Schizophrenia Risk Genes. (2017)
  • Author(s): Paparelli A, Iwata K, Wakuda T, Iyegbe C, Murray RM, Takei N.
  • Journal Title: Front Mol Neurosci Volume: 10 Pages: 341-341
  • DOI: 10.3389/fnmol.2017.00341
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 統合失調症におけるα7ニコチン性アセチルコリン受容体：[11C](R)-MeQAAを用いたPET脳画像の予備的研究 (2019)
  • Author(s): 和久田智靖、横倉正倫、中泉享子、加藤康彦、亀野陽亮、桑原斉、二ツ橋昌実、吉川悦次、間賀田泰寛、尾内康臣、武井教使、山末英典
  • Organizer: 第115回日本精神神経学会学術総会
• [Presentation] A PILOT STUDY OF [11C] (R)-MEQAA PET BRAIN IMAGING ANALYSIS OF ALPHA 7 NICOTINIC ACETYLCHOLINE RECEPTORS AVAILABILITY IN SCHIZOPHRENIA (2018)
  • Author(s): Wakuda Tomoyasu, Yokokura Masamichi, Nakaizumi Kyoko, Kato Yasuhiko, Kameno Yosuke, Futatsubashi Masami, Yoshikawa Etsuji, Magata Yasuhiro, Ouchi Yasuomi, Yamasue Hidenori, Takei Nori
  • Organizer: The 6th Biennial Schizophrenia International Research Society Conference
  • Int'l Joint Research