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論文
- タイトル
- タイトル（英）
- Hyper-maturity and accelerated aging in the hippocampus of mouse models of neuropsychiatric disorders with anxiety-like behavior
- 参照URL
- https://researchmap.jp/kazutakaikeda/published_papers/53273490
- 著者
- 著者（英）
- Hideo Hagihara,Hisatsugu Koshimizu,Satoko Hattori,Hirotaka Shoji,Miho Tanaka,Kazutaka Ikeda,Tsuyoshi Miyakawa
- 担当区分
- 概要
- 概要（英）
- Abstract Proper maturation of neuronal and glial cells in the hippocampus is essential for emotional regulation and cognitive function. While pseudo-immaturity, defined as arrested or reversed development, has been extensively implicated in various neuropsychiatric conditions, the opposite phenomenon, hyper-maturity, remains underexplored. Here, we present transcriptomic evidence of hippocampal hyper-maturity across 17 datasets from 16 mouse models with genetic, pharmacological, or other experimental manipulations, identified through a comprehensive screening of over 260,000 omics datasets. These models were characterized by a pronounced overrepresentation of gene expression changes typically observed during postnatal development and included serotonin transporter knockout mice, glucocorticoid receptor overexpressing mice, and corticosterone-treated mice, models of depression and anxiety, Df(16)A <sup>+/−</sup> mice, a 22q11.2 deletion schizophrenia model, β-glucuronidase-deficient lysosomal storage disorder model mice, and senescence-prone SAMP8 mice. Meta-analysis of enriched pathways highlighted associations of synapse-related genes with the hyper-maturity signature. Behavioral annotations from public datasets further suggest that hippocampal hyper-maturity models predominantly exhibit increased anxiety-like behaviors, whereas immaturity models tend to display the opposite pattern. Notably, hippocampal hyper-maturity encompassed two transcriptional dimensions: enhanced postnatal development and accelerated aging. For example, SAMP8 mice aligned more with developmental enhancement, whereas corticosterone-treated and lysosomal storage disorder models reflected aging acceleration. Combined analysis with available single-cell RNA-sequencing data further delineated that microglia and granule cells may contribute to aging-associated transcriptional shifts. These findings suggest that hippocampal hyper-maturity and accelerated aging represent convergent molecular phenotypes associated with anxiety-like behavior. Bidirectional alterations in hippocampal maturity may serve as a transdiagnostic endophenotype and offer novel therapeutic or anti-aging targets for neuropsychiatric disorders.
- 出版者・発行元
- 出版者・発行元（英）
- Springer Science and Business Media LLC
- 誌名
- 誌名（英）
- Neuropsychopharmacology
- 巻
- 51
- 号
- 5
- 開始ページ
- 856
- 終了ページ
- 867
- 出版年月
- 2025年10月27日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 0893-133X
- DOI URL
- https://doi.org/10.1038/s41386-025-02237-6
- 共同研究・競争的資金等の研究課題
研究者
池田 和隆
(イケダ カズタカ)