Pharmacotherapeutic strategies from the elucidation of mechanisms underlying postnatal stress-induced neurodevelopmental dysfunction and parental behavior

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07133
• 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: Nagasaki International University
• Principal Investigator: Yamaguchi Taku 長崎国際大学, 薬学部, 教授 (80325563)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 神経発達障害 / 幼若期ストレス / 抑うつ様行動 / 養育行動 / 選択的セロトニン再取り込み阻害薬 / 薬物治療 / DNAマイクロアレイ / 網羅的遺伝子発現解析

Outline of Final Research Achievements

Depressive-like behaviors in rats exposed to pharmacological stress (namely ACTH administration) during the early postnatal period were possibly ameliorated by the maternal or foster care during the developmental period and were also ameliorated by therapeutic (treatment immediately after exposure to stress) or preventive (treatment during the mature period when depressive-like behaviors develop) administration of the selective serotonin reuptake inhibitor fluvoxamine, by behavioral analysis to evaluate depressive-like behaviors (sucrose preference test and Splash test). Furthermore, the expression of late-onset depressive-like behaviors in rats exposed to pharmacological stress during the early postnatal period suggested the involvement of a specific group of genes that show a time-specific expression pattern in the prefrontal cortex, according to the results of a comparative gene expression analysis.

Free Research Field

神経精神薬理学・行動薬理学

Academic Significance and Societal Importance of the Research Achievements

幼若期ストレスモデルラットが示す成長後の抑うつ様行動は、発達期に母獣あるいは里親による哺育によって改善する可能性、および抗うつ薬の治療的あるいは予防的投与によっても改善した。これらの知見は、幼若期に曝露された過剰なストレスによる成長後の情動機能異常(例えば、抑うつ症状)の改善に、薬物療法（抗うつ薬）による治療介入のみならず、非薬物療法としての養育的介入の有用性を示唆すると考える。また、幼若期ACTH群に認められる遅延性の抑うつ様行動の発現は、時期特異的な発現パターンを示す脳内遺伝子群が関与することから、今後、その新たな脳内候補分子をターゲットとした治療戦略が期待される。