Comprehensive search of Treatment-resistant depression associated protein by time-controlled transcardiac perfusion cross-linking technique

• Project/Area Number: 22591259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: OHSHIRO Masaya 浜松医科大学, 医学部, 特任研究員 (40567880)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Katsuaki 浜松医科大学, 医学部, 准教授 (00285040) ; IWATA Keiko 福井大学, 子どものこころの発達研究センター, 助教研究者番 (30415088) ; TACHIBANA Taro 大阪市立大学, 工学研究科, 准教授 (80311752) ; 中村 和彦 浜松医科大学, 医学部, 准教授 (80263911) ; 松崎 秀夫 浜松医科大学, 子どものこころの発達研究センター, 准教授 (00334970)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: うつ病 / セロトニン・トランスポーター / 治療抵抗性 / 中枢神経系 / In vivo cross-link 法 / In vivo cross-link法

Research Abstract

Change in serotonin transporter (SERT) function may be implicated in treatment-resistant depression. Anti-depressant, serotonin selective reuptake inhibitor (SSRI) is acting on SERT present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. In this study, we have searched for novel SERT -binding proteins by time-controlled transcardiac perfusion cross-linking and a pull-down system, and investigated whether the expression of one such protein inhibited the effect of SSRI on serotonergic neuron.N-ethylmaleimide-sensitive factor (NSF) was identified by a pull-down system as a novel SERT -binding protein. Alterations of SERT function and membrane expression upon knockdown of the novel SERT -binding protein were studied in HEK293-hSERT cells. NSF co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and its uptake function. NSF endogenously co-localized with SERT and interacted with SERT. Time-controlled transcardiac perfusion cross-linking technique has screened 85 candidate proteins. Then, 14 proteins have identified from the candidates by shot-gun analysis score. Endogenous interaction of SERT with 14 proteins, NSF and Syntaxin 1A wereevaluated in mouse primary cultured raphe neurons. The association between proteinsand treatment-resistant depression have not evaluated within this term of grant-in-aid.

Research Products

• [Journal Article] Reduced expression of apolipoprotein E receptor type 2 in peripheral blood lymphocytes from patients with major depressive disorder. (2010)
  • Author(s): Suzuki K, Iwata Y, Matsuzaki H, Anitha A, Suda S, Iwata K, Shinmura C, Kameno Y, Tsuchiya KJ, Nakamura K, Takei N, Mori N.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry. Volume: 34(6) Pages: 1007-1010
  • Peer Reviewed
• [Presentation] 急性ストレスモデルにおける局所脳血流・脳糖代謝解析 (2012)
  • Author(s): 亀野 陽亮, 松崎 秀夫, 高橋 健二, 岩田 圭子, 鈴木 勝昭, 間賀田 泰寛, 森 則夫
  • Organizer: 第39回日本脳科学会
  • Place of Presentation: 北九州市
• [Remarks] 浜松医科大学・精神医学講座
  • URL: http://hmup.jpn.org/