情動を制御するBDNFの直接効果の解明

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15H03123
• Research Institution: Keio University
• Principal Investigator: 田中 謙二 慶應義塾大学, 医学部(信濃町), 准教授 (30329700)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: BDNF / ストレス / うつ病

Outline of Annual Research Achievements

雄同士の攻撃性が高まるBDNF mRNA isoform 1,2,3ノックダウンマウスを用いて、餌報酬を強化子とするオペラント条件付けを行った。攻撃性の亢進は意思決定の何らかの異常が背景にあると考えられたので、意思決定を含めたマウスの高次機能を広くスクリーニングできる3-choice serial reaction time taskで何らかの異常を検出できると考えた。しかしこのタスクではBDNF isoform 1,2,3ノックダウンマウスの高次脳機能の突出した異常を検出することは出来なかった。次いで、BDNFシグナルの低下がストレス応答をどのように変化させるのか調べる目的で、涙の分泌量を調べた。涙の分泌量はストレス負荷時に低下し、ストレス解除後に分泌量が正常化する。豊かな環境で飼育すると、涙の基礎分泌量に変化は無いが、ストレス負荷時に見られるはずの涙分泌量低下が起こらなくなる。つまりレジリエントになる。ストレス応答、ストレス抵抗性、ストレスからの回復にBDNFがどのように関与しているか各ノックダウンマウスを用いて調べた。isoform 1,2,3ノックダウンでは、ストレス負荷前から涙の分泌が低かった。isoform 4,5,6,7ノックダウンマウスでは基礎分泌量は正常であった。isoform 4,5,6,7ノックダウンマウスは、豊かな環境であってもストレス負荷時に涙の分泌量が低下した。このことから、涙の分泌を表現型とした場合のストレス抵抗性、ストレス負荷後の回復には、BDNF isoform 4,5,6,7が関与することが示された。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

BDNFのisoformごとの機能を、うつ、不安、認知機能、ストレス応答など、多面的に検討することが出来ている。

Strategy for Future Research Activity

より生理的な条件でマウスの認知機能を評価する実験系を取り入れ、BDNFが認知機能、高次脳機能に及ぼす直接的な効果を解明する。

Research Products

• [Int'l Joint Research] University Texas, Austin/University of Pittsburgh/Columbia University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: University Texas, Austin/University of Pittsburgh/Columbia University
  • # of Other Institutions: 1
• [Int'l Joint Research] Universite Libre de Bruxelles(ベルギー)
  • Country Name: BELGIUM
  • Counterpart Institution: Universite Libre de Bruxelles
• [Int'l Joint Research] Ottawa Hospital Research Institute(Canada)
  • Country Name: Canada
  • Counterpart Institution: Ottawa Hospital Research Institute
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• [Journal Article] High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates. (2017)
  • Author(s): Seiriki K, Kasai A, Hashimoto T, Schulze W, Niu M, Yamaguchi S, Nakazawa T, Inoue KI, Uezono S, Takada M, Naka Y, Igarashi H, Tanuma M, Waschek JA, Ago Y, Tanaka KF, Hayata-Takano A, Nagayasu K, Shintani N, Hashimoto R, Kunii Y, Hino M, Matsumoto J, Yabe H, Nagai T, Fujita K, Matsuda T, Takuma K, Baba A, Hashimoto H.
  • Journal Title: Neuron Volume: 94 Pages: 1085-1100
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• [Journal Article] Association of impaired neuronal migration with cognitive deficits in extremely preterm infants. (2017)
  • Author(s): Kubo KI, Deguchi K, Nagai T, Ito Y, Yoshida K, Endo T, Benner S, Shan W, Kitazawa A, Aramaki M, Ishii K, Shin M, Matsunaga Y, Hayashi K, Kakeyama M, Tohyama C, Tanaka KF, Tanaka K, Takashima S, Nakayama M, Itoh M, Hirata Y, Antalffy B, Armstrong DD, Yamada K, Inoue K, Nakajima K.
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• [Journal Article] Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity. (2017)
  • Author(s): Natsubori A, Tsutsui-Kimura I, Nishida H, Bouchekioua Y, Sekiya H, Uchigashima M, Watanabe M, de Kerchove d'Exaerde A, Mimura M, Takata N, Tanaka KF.
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• [Journal Article] 強迫症研究のこれからtranslational researchの可能性について (2017)
  • Author(s): 酒井 雄希, 田中 謙二
  • Journal Title: 精神科治療学 Volume: 32 Pages: 399-404
• [Presentation] 光観察と光操作を組み合わせた意欲行動研究 (2017)
  • Author(s): 田中謙二
  • Organizer: 第2回 ルミノジェネティクス研究会
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• [Presentation] Oligodendrocyte is a dynamic modulator of conduction velocity (2017)
  • Author(s): 田中謙二、山崎良彦
  • Organizer: 第60回 日本神経化学会
• [Presentation] 島皮質-線条体回路と意欲行動 (2017)
  • Author(s): 田中謙二
  • Organizer: 第5回 心身医学のニューロサイエンス研究会
  • Invited
• [Presentation] 光操作・光計測 (2017)
  • Author(s): 田中謙二
  • Organizer: 第４９回藤田学園医学会・研究最前線セミナー
  • Invited
• [Presentation] Fiberphotometry (2017)
  • Author(s): 田中謙二
  • Organizer: 第28回 マイクロダイアリシス研究会
  • Invited
• [Presentation] 意欲行動の開始を支配する島皮質-線条体回路 (2017)
  • Author(s): 田中謙二
  • Organizer: 次世代脳 新学術領域合同シンポジウム
  • Invited