Research Project
Grant-in-Aid for Scientific Research (C)
うつ病は、長期にわたる抑うつ症状や、意欲の低下などを主症状とする精神疾患であり、本邦を含む先進国において大きな社会問題となっている。本研究では、セロトニン神経に着目し、その活動計測/活動への介入を用いて、セロトニン神経活動変化がうつ症状表出/消失の決定因子であるという仮説を検証するとともに、その活動変化の「臨界点」およびその分子メカニズムの解明に挑む。
Using optogenetic techniques, we investigated whether chronic activation of serotonergic neurons in the dorsal raphe nucleus (DRN) causes persistent antidepressant effects. We found that chronic activation of DRN serotonergic neurons induces persistent antidepressant effects and that the mechanism is selective activation of the pleasant experience neural ensemble in the hippocampus. Furthermore, we found that the median raphe nucleus (MRN) serotonergic neurons are responsible for unpleasant emotions, in contrast to the DRN serotonergic neurons. These results suggest that among serotonergic neurons, the DRN serotonergic neurons play a central role in antidepressant effects and that the MRN serotonergic neurons may have an antagonistic role.
本研究により明らかにされた、背側縫線核セロトニン神経と正中縫線核セロトニン神経の機能的対照性と、背側縫線核セロトニン神経による持続的な抗うつ作用を併せて考えると、セロトニン神経伝達を個別に制御が可能な薬剤を開発することで、既存薬を超える抗うつ薬開発が可能になると考えられることから、本研究によりその基礎的知見が得られたものと考えられる。
All 2024 2023 2022 2021 2020 Other
All Int'l Joint Research (2 results) Journal Article (31 results) (of which Int'l Joint Research: 10 results, Peer Reviewed: 31 results, Open Access: 26 results) Presentation (3 results) (of which Invited: 3 results) Remarks (5 results)
Biological and Pharmaceutical Bulletin
Volume: 47 Issue: 1 Pages: 253-258
10.1248/bpb.b23-00828
Translational Psychiatry
Volume: 14 Issue: 1 Pages: 27-27
10.1038/s41398-024-02731-3
Volume: 46 Issue: 1 Pages: 102-110
10.1248/bpb.b22-00668
Molecular Neurobiology
Volume: 60 Issue: 12 Pages: 6931-6948
10.1007/s12035-023-03519-0
Science Advances
Volume: 9 Issue: 29 Pages: 29-29
10.1126/sciadv.adh0102
Drug Safety
Volume: - Issue: 4 Pages: 371-389
10.1007/s40264-023-01278-4
Cell Reports
Volume: 42 Issue: 3 Pages: 112149-112149
10.1016/j.celrep.2023.112149
Frontiers in Pharmacology
Volume: 14 Pages: 1137952-1137952
10.3389/fphar.2023.1137952
Volume: 14 Pages: 1135516-1135516
10.3389/fphar.2023.1135516
International Journal of Molecular Sciences
Volume: 24 Issue: 4 Pages: 3465-3465
10.3390/ijms24043465
Frontiers in Neuroscience
Volume: 16 Pages: 1082375-1082375
10.3389/fnins.2022.1082375
Frontiers in Immunology
Volume: 13 Pages: 1084960-1084960
10.3389/fimmu.2022.1084960
Journal of Pharmacological Sciences
Volume: 151 Issue: 1 Pages: 9-16
10.1016/j.jphs.2022.10.006
Nature Communications
Volume: 13 Issue: 1 Pages: 7708-7708
10.1038/s41467-022-35346-7
iScience
Volume: 25 Issue: 10 Pages: 105228-105228
10.1016/j.isci.2022.105228
Glia
Volume: 70 Issue: 9 Pages: 1666-1680
10.1002/glia.24188
Volume: 8 Issue: 11
10.1126/sciadv.abi6375
Sci Adv.
Volume: 8
Neuropharmacology
Volume: 206 Pages: 108926-108926
10.1016/j.neuropharm.2021.108926
Volume: 148 Issue: 3 Pages: 295-299
10.1016/j.jphs.2022.01.004
Volume: 44 Issue: 2 Pages: 181-187
10.1248/bpb.b20-00510
130007979613
Volume: 11 Issue: 1 Pages: 548-548
10.1038/s41398-021-01676-1
Volume: 12 Pages: 635293-635293
10.3389/fphar.2021.635293
Biochemical and Biophysical Research Communications
Volume: 568 Pages: 167-173
10.1016/j.bbrc.2021.06.058
Commun. Biol.
Volume: 4 Issue: 4 Pages: 599-599
10.1016/j.jphs.2021.04.006
JCI Insight
Volume: in press Issue: 10 Pages: 1-16
10.1172/jci.insight.145632
120007038817
Cancer Research
Volume: 81 Issue: 8 Pages: 2207-2219
10.1158/0008-5472.can-20-2799
Scientific Reports
Volume: 11 Issue: 1 Pages: 525-525
10.1038/s41598-020-80113-7
120006951708
Volume: 529 Issue: 3 Pages: 590-595
10.1016/j.bbrc.2020.06.103
Volume: 166 Pages: 107968-107968
10.1016/j.neuropharm.2020.107968
Volume: 21 Issue: 6 Pages: 2160-2160
10.3390/ijms21062160
120006826701
https://molpharm.pharm.kyoto-u.ac.jp/
https://molpharm.pharm.kyoto-u.ac.jp/molpharm/
https://www.kyoto-u.ac.jp/ja/research-news/2022-12-23-0
https://www.kyoto-u.ac.jp/ja/research-news/2023-02-28-1
https://www.pharm.kyoto-u.ac.jp/channel/