Elucidation of antidepressant signals by targeting differentiation and maturation factors in hippocampal neurons

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Segi Eri 東京理科大学, 先進工学部生命システム工学科, 教授 (70378628)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: うつ病 / 海馬 / 歯状回 / 神経新生 / ストレス / 成熟

Outline of Final Research Achievements

We hypothesized that functional changes in the hippocampal dentate gyrus by antidepressant treatment contribute to antidepressant-like behavior and aimed to clarify the proliferation/differentiation/maturation signals in the hippocampus induced by antidepressant treatment and their effects on behaviors. The analysis of this study revealed that (1) activation of the transcription factor SRF is important for modulation of hippocampal function by electroconvulsive stimulation, (2) the maturation marker calbindin and desmoplakin in the dentate gyrus is the factors maintaining neural activity, neurogenesis and anti-anxiety, (3) novel antidepressant signals via noradrenaline-D1 receptors (4) increased expression of mature neuronal markers occurs in models of depression (5) survival of new-born neurons is associated with anxiety-like behavior.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、歯状回の神経活性化や神経新生などの機能変化が抗うつ様行動に寄与するとともに、不安行動の表出にも関わることを新たに見出した。今後、成熟神経の刺激応答性を明らかにしていくことが、うつ/不安の治療標的の同定につながるものと期待される。