2022 Fiscal Year Final Research Report
Understanding the treatment of cognitive dysfunction in depression: delta-opioid receptor-mediated mechanisms of improvement.
Project/Area Number |
20K07978
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52030:Psychiatry-related
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Research Institution | Kitasato University |
Principal Investigator |
Iwai Takashi 北里大学, 薬学部, 講師 (90339135)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | うつ病 / オピオイド / 認知機能 / GABA / 海馬 / ストレス |
Outline of Final Research Achievements |
In this study, we investigated the effects of the δ-opioid receptor inverse agonist SYK-623 on Antidepressant-Resistant Chronic Mild Stress (ACMS) mice, a model unresponsive to antidepressants. SYK-623 was found to inhibit the induction of learning-memory impairments and depressive-like behaviors in ACMS mice. In the hippocampus, a crucial brain region for the regulation of learning-memory and stress responses, ACMS mice demonstrated a reduction in the number of GABA neurons, the expression of GABA synthesizing enzyme (GAD), and the density of GAD-positive nerve fibers compared to normal mice, suggesting the induction of GABAergic neuronal damage. SYK-623 was shown to inhibit these stress-induced GABAergic neuronal damages and exert a protective effect on GABAergic neurons against chronic stress, providing novel insights for potential therapeutic strategies.
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Free Research Field |
精神薬理学
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Academic Significance and Societal Importance of the Research Achievements |
うつ病患者の認知機能の低下は、気分の症状と比べて治療効果が見られにくく、治療期間の長期化、再発の要因となる。本研究ではδオピオイド受容体を介して、ストレスによるGABA神経障害を抑制することが、認知機能の改善に寄与する可能性を示唆した。この事により、従来の抗うつ薬とは異なるアプローチによりうつ病患者の脳機能を改善させる治療の開発につながることが期待される。さらに、認知機能と同様に、うつ病患者の寛解後にも残存する睡眠障害に対しても有効性を示唆する結果が得られ、本研究の成果が、うつ病治療のさまざまな側面に波及すると考えられる。
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