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論文
- タイトル
- タイトル（英）
- Pentosidine accumulation induced by Akr1a deficiency drives aggression and hyperactivity.
- 参照URL
- https://researchmap.jp/toriumi1207/published_papers/52243974
- 著者
- 著者（英）
- Kyoka Iino,Kazuya Toriumi,Mitsuhiro Miyashita,Kazuhiro Suzuki,Koichi Tabata,Satoshi Miyata,Motoko Takahashi,Junichi Fujii,Masanari Itokawa,Makoto Arai
- 担当区分
- 責任著者
- 概要
- 概要（英）
- Advanced glycation end products (AGEs) are a heterogeneous group of glycation-derived compounds that accumulate under metabolic stress and contribute to age-related and chronic diseases. Pentosidine (PEN), a well-characterized fluorescent AGE, increases during aging under certain pathological conditions. In particular, increased PEN levels have been observed in a subset of patients with schizophrenia and are associated with more severe clinical outcomes. Glucuronic acid (GlcA) has previously been identified as a metabolic precursor of PEN, and impaired GlcA metabolism due to reduced aldo-keto reductase family 1 member A1 (AKR1A1) activity may underlie PEN accumulation. In the present study, to investigate the neurobiological impact of endogenous PEN accumulation, we examined neurobehavioral consequences using Akr1a knockout (KO) mice, which exhibit impaired GlcA metabolism. These mice exhibited significantly elevated PEN levels in both the plasma and prefrontal cortex (Pfc), a brain region critically involved in higher-order cognitive and behavioral regulation, accompanied by increased aggression and hyperactivity-behavioral domains relevant to patients with schizophrenia. Notably, aggression measures were positively correlated with PEN concentrations, whereas PEN levels were associated with novelty-driven exploratory locomotion but not with sustained baseline locomotor activity. Transcriptomic analysis of Pfc revealed altered expression of genes involved in guanylate cyclase signaling, cytoskeletal organization, and the immune response. Cyclic guanosine monophosphate (cGMP) levels were significantly reduced, suggesting impaired downstream signaling. Together, these findings demonstrate that GlcA-driven PEN accumulation induces molecular and behavioral alterations in the brain and provides a dimensional mouse model linking glycation-related metabolic stress to aggression and hyperactivity relevant to schizophrenia.
- 出版者・発行元
- 出版者・発行元（英）
- Elsevier BV
- 誌名
- 誌名（英）
- Neuroscience letters
- 巻
- 877
- 号
- 開始ページ
- 138557
- 終了ページ
- 138557
- 出版年月
- 2026年2月21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
- 0304-3940
- DOI URL
- https://doi.org/10.1016/j.neulet.2026.138557
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