Study on the astrocyte-derived TSP-1 as an ECT target molecule of refractory depression.

• Project/Area Number: 16K18883
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Department of Clinical Research, National Hospital Organization Kure Medical Center
• Principal Investigator: Okada-Tsuchioka Mami 独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, 研究員(移行) (30517280)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シナプス新生 / うつ病 / アストロサイト / thrombospondin-1 / 電気けいれん療法

Outline of Final Research Achievements

I have focused on synaptogenesis-related factor, thrombospondin-1 (TSP-1), as a novel target molecule of refractory depression. The aim of this study was to clarify how TSP-1 contributes to the pathology of depression and the action of electroconvulsive therapy (ECT). Serum TSP-1 in patients with refractory depression showed a significant decrease specific to female patients but did not change before and after ECT. These results suggest that TSP-1 in serum is possible to be a gender-dependent trait marker.
As basic research, synaptogenesis-related gene expression was investigated in the hippocampus of the male chronically corticosterone-administered depression model, but no significant change was observed. It seems necessary to investigate focusing on gender difference in the future.

Research Products

• [Journal Article] Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT) (2017)
  • Author(s): Shibasaki Chiyo、Itagaki Kei、Abe Hiromi、Kajitani Naoto、Okada-Tsuchioka Mami、Takebayashi Minoru
  • Journal Title: International Journal of Neuropsychopharmacology Volume: 21 Issue: 3 Pages: 236-241
  • DOI: 10.1093/ijnp/pyx086
  • Peer Reviewed / Open Access
• [Journal Article] Factors associated with relapse after a response to electroconvulsive therapy in unipolar versus bipolar depression. (2017)
  • Author(s): Itagaki K, Takebayashi M, Shibasaki C, Kajitani N, Abe H, Okada-Tsuchioka M, Yamawaki S.
  • Journal Title: Journal of Affective Disorders. Volume: 208 Pages: 113-119
  • DOI: 10.1016/j.jad.2016.08.047
  • Peer Reviewed
• [Journal Article] Identification of lysophosphatidic acid receptor 1 in astroglial cells as a target for glial cell line-derived neurotrophic factor expression induced by antidepressants. (2016)
  • Author(s): Kajitani, N., Miyano, K., Okada-Tsuchioka, M., Abe, H., Itagaki, K., Hisaoka-Nakashima, K., Morioka, N., Uezono, Y., Takebayashi, M.
  • Journal Title: J Biol Chem Volume: 291 Issue: 53 Pages: 27364-27370
  • DOI: 10.1074/jbc.m116.753871
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The expression of glial cell line-derived neurotrophic factor mRNA by antidepressants involves matrix metalloproteinase-9 activation in rat astroglial cells (2016)
  • Author(s): Abe H, Hisaoka-Nakashima K, Kajitani N, Okada-Tsuchioka M, Yano R, Itagaki K, Shibasaki C, Morioka N, Nakata Y, Takebayashi M
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 479 Issue: 4 Pages: 907-912
  • DOI: 10.1016/j.bbrc.2016.09.070
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] アストロサイトを標的とした新たな抗うつ薬の作用点としてのLPA1の可能性 (2017)
  • Author(s): 岡田麻美、梶谷直人、宮野加奈子、安部裕美、大盛 航、板垣 圭、上園保仁、竹林 実
  • Organizer: 第36回躁うつ病の薬理・生化学的研究懇話会
• [Book] Advances in modern medicine (2016)
  • Author(s): Taniyama K and Kamiike W
  • Total Pages: 488
  • Publisher: Bentham Science