Identification and pharmacological control of serotonergic projection involved in decision making
| Project/Area Number |
16H05091
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Kaneko Shuji 京都大学, 薬学研究科, 教授 (60177516)
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| Co-Investigator(Kenkyū-buntansha) |
永安 一樹 京都大学, 薬学研究科, 助教 (00717902)
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| Research Collaborator |
Nakagawa Takayuki
Shirakawa Hisashi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | セロトニン / ウイルスベクター / うつ病 / 強迫性障害 / 精神疾患 / ドパミン / 意思決定 / 光遺伝学 / 神経薬理学 |
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| Outline of Final Research Achievements |
Major depression is a social and economic burden worldwide. Serotonergic signaling has been implicated in the pathophysiology of this disorder. Moreover, clinical studies have indicated that ketamine has a potent antidepressive efficacy. However, the precise mechanisms underlying major depression are still unclear. Here, we used viral vectors capable of efficient and specific transduction of serotonergic neurons in mice and rats for elucidation of serotonergic roles in depression-like behaviors. We found that ketamine activated dorsal raphe serotonin neurons via activation of acetylcholine neurons in the pedunculopontine tegmental nucleus. We also found that acute activation of serotonergic neurons in the dorsal raphe nucleus increases anti-depressive like behaviors in rats and mice. These findings further our understanding of the pathophysiological role of dorsal raphe serotonergic neurons in different species and the role of these neurons as therapeutic targets in major depression.
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| Academic Significance and Societal Importance of the Research Achievements |
うつ病や不安障害などの精神疾患は、本邦を含む先進国において、極めて重大な社会問題となっている疾患である。本研究は、極めて効果が高いうつ病の治療薬として近年研究が進んでいるケタミンの作用において、アセチルコリン神経核である脚橋被蓋核が極めて重要な役割を果たしている可能性を見出した。また、光遺伝学的手法を用いることで、背側縫線核セロトニン神経を活性化するだけで、抗うつ作用が引き起こされることを明らかにした。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] TRPM2 confers susceptibility to social stress but is essential for behavioral flexibility.2019
Author(s)
Andoh C, Nishitani N, Hashimoto E, Nagai Y, Takao K, Miyakawa T, Nakagawa T, Mori Y, Nagayasu K, Shirakawa H, Kaneko S.
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Journal Title
Brain Res.
Volume: 1704
Pages: 68-77
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats.2018
Author(s)
Nishitani N, Nagayasu K, Asaoka N, Yamashiro M, Andoh C, Nagai Y, Kinoshita H, Kawai H, Shibui N, Liu B, Hewinson J, Shirakawa H, Nakagawa T, Hashimoto H, Kasparov S, Kaneko S.
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Journal Title
Neuropsychopharmacology
Volume: 44
Issue: 4
Pages: 721-732
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A rat long-lasting cystitis model induced by intravesical injection of hydrogen peroxide.2017
Author(s)
Dogishi K, Okamoto K, Majima T, Konishi-Shiotsu S, Homan T, Kodera M, Oyama S, Oyama T, Shirakawa H, Yoshimura N, Nakagawa T, Kaneko S.
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Journal Title
Physiol Rep.
Volume: 5
Issue: 4
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS.2016
Author(s)
Miyake T, Nakamura S, Zhao M, So K, Inoue K, Numata T, Takahashi N, Shirakawa H, Mori Y, Nakagawa T, Kaneko S
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Journal Title
Nature Communications
Volume: 7
Issue: 1
Pages: 12840-12840
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Hypoxia-induced sensitization of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice2016
Author(s)
So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, Imai S, Mori Y, Nakagawa T, Matsubara K, Kaneko S
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 23261-23261
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] The regulatory effect of oxaliplatin on human TRPA1 cold sensitivity2017
Author(s)
Takahito Miyake, Saki Nakamura, Meng Zhao, Kanako So, Keisuke Inoue, Tomohiro Numata, Nobuaki Takahashi, Hisashi Shirakawa, Yasuo Mori, Takayuki Nakagawa, Shuji Kaneko
Organizer
第90回日本薬理学会年会
Place of Presentation
長崎県
Year and Date
2017-03-16
Related Report
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[Presentation] Preferential demyelination accompanied with Schwann cell dedifferentiation by microtubule inhibitors participates in the chemotherapy-induced peripheral neuropathy2017
Author(s)
Mayuna Matsumoto, Satoshi Imai, Madoka Koyanagi, Yui Nakazato, Ziauddin Azimi, Atsushi Yonezawa, Tomohiro Omura, Shunsaku Nakagawa, Shuji Kaneko, Takayuki Nakagawa, Kazuo Matsubara
Organizer
第90回日本薬理学会年会
Place of Presentation
長崎県
Year and Date
2017-03-15
Related Report
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[Presentation] 社会的挫折ストレス負荷によるうつ病モデルマウスにおけるベンゾジ アゼピン系睡眠薬による睡眠作用の効力変化2016
Author(s)
辻 光貴, 今井 哲司, 宮山 大, 清水 佑美, 重面 雄紀, 西谷 直也, 米澤 淳, 大村 友博, 中川 俊作, 金子 周司, 中川 貴之, 松原 和夫
Organizer
第130回日本薬理学会近畿部会
Place of Presentation
京都府
Year and Date
2016-11-19
Related Report
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[Presentation] Rellief from Prolyl Hydroxylation by Oxaliplatin Allows TRPA1 tp sense Noxious Cold via Transduction of Reactive Pxigen Species Signaling2016
Author(s)
Miyake, T., Nakamura, S., Zhao, M., So, K., Shirakawa, H., Mori, Y., Nakagawa, T., Kaneko, S
Organizer
IASP 16th world congress
Place of Presentation
神奈川県
Year and Date
2016-09-26
Related Report
Int'l Joint Research
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