Research Project
Grant-in-Aid for Scientific Research (C)
現在病院で処方されている抗うつ薬は、即効性がなく、効果が得られるまでに数週間以上の服用が必要であり、約3割の患者には効果がないため、新たな抗うつ薬の創出が求められている。私たちは、体内でDHAやEPAを原料にして生成されるレゾルビン類という物質に着目し、これまでにレゾルビン類を脳内に直接投与すると即効性の抗うつ効果が得られることを明らかにしてきた。本研究では、レゾルビン類の臨床応用を見据え、これらの点鼻薬が、既存の抗うつ薬が効かないうつ病にも有効か否かを調べるとともに、その作用メカニズムを明らかにすることを目的とする。
In this study, we found that intranasal (i.n.) administration of resolvin E1 (RvE1), a bioactive lipid mediator derived from EPA, produces antidepressant-like effects via BDNF/VEGF release and the subsequent activation of mTORC1 in the medial prefrontal cortex (mPFC) in mouse models of depression, including a treatment-resistant depression model. We also found that intraperitoneal and oral administration of o-BZ-RvE2, a metabolically stable analog of resolvin E2, an EPA metabolite, produces antidepressant-like effects via mTORC1 activation in the mPFC. These findings suggest that i.n. administration is a viable and promising route for the delivery of unstable resolvins to the brain and can pave the way for the application of resolvins in the treatment of depression. Moreover, this study suggests that stable resolvin analogs could be lead compounds for novel antidepressants.
うつ病の患者数は世界で約2.8億人と言われ、深刻な社会的・経済的損失をもたらしている。一方、既存の抗うつ薬は効果発現が遅く、3割の患者が治療抵抗性を示すため、新たな抗うつ薬の開発が喫緊の課題である。本研究の成果により、レゾルビン類やその誘導体が新たな抗うつ薬候補化合物として有望であることが示唆された。
All 2022 2021 2020 2019 Other
All Journal Article (19 results) (of which Int'l Joint Research: 5 results, Peer Reviewed: 19 results, Open Access: 8 results) Presentation (44 results) (of which Int'l Joint Research: 2 results, Invited: 4 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)
Behavioural Brain Research
Volume: 418 Pages: 113676-113676
10.1016/j.bbr.2021.113676
Biological and Pharmaceutical Bulletin
Volume: 44 Issue: 10 Pages: 1548-1550
10.1248/bpb.b21-00461
130008095750
Volume: 44 Issue: 7 Pages: 1007-1013
10.1248/bpb.b21-00314
130008060342
Volume: 44 Issue: 5 Pages: 724-731
10.1248/bpb.b21-00137
130008033248
Neuropsychopharmacology Reports
Volume: 41 Issue: 3 Pages: 426-429
10.1002/npr2.12198
Journal of Pharmacological Sciences
Volume: 147 Issue: 1 Pages: 58-61
10.1016/j.jphs.2021.05.009
Volume: 147 Issue: 1 Pages: 33-39
10.1016/j.jphs.2021.05.002
Neuroscience Letters
Volume: 743 Pages: 135555-135555
10.1016/j.neulet.2020.135555
Volume: 394 Pages: 112844-112844
10.1016/j.bbr.2020.112844
Folia Pharmacologica Japonica
Volume: 155 Issue: 6 Pages: 381-385
10.1254/fpj.20044
130007933842
Volume: 40 Issue: 3 Pages: 297-301
10.1002/npr2.12124
Volume: 155 Issue: 3 Pages: 135-139
10.1254/fpj.19147
130007839047
Neuropharmacology
Volume: 166 Pages: 107968-107968
10.1016/j.neuropharm.2020.107968
European Neuropsychopharmacology
Volume: 31 Pages: 145-151
10.1016/j.euroneuro.2019.11.002
Pharmacology Biochemistry and Behavior
Volume: 188 Pages: 172837-172837
10.1016/j.pbb.2019.172837
European Journal of Neuroscience
Volume: - Issue: 1 Pages: 126-139
10.1111/ejn.14630
Psychopharmacology
Volume: 印刷中 Issue: 7 Pages: 2235-2242
10.1007/s00213-019-05222-2
Biological Psychiatry
Volume: 86 Issue: 2 Pages: 143-152
10.1016/j.biopsych.2018.12.014
American Journal of Psychiatry
Volume: 176 Issue: 5 Pages: 388-400
10.1176/appi.ajp.2018.17121368
http://www.p.kanazawa-u.ac.jp/~yakuri/