A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders

Abstract Polysialic acid (polySia), a glycoepitope critical for neural development and plasticity, remains difficult to quantify owing to its structural complexity. Here, we present a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) utilizing novel probes to measure polySia expres...

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Main Authors: Masaya Hane, Ayane Naramura, Kaito Hayakawa, Chikara Abe, Takahiro Nakagawa, Itaru Kushima, Soma Furukawa, Yuki Fukami, Keisuke Ikegami, Kazumasa Saigoh, Susumu Kusunoki, Masahisa Katsuno, Norio Ozaki, Ken Kitajima, Chihiro Sato
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-02583-x
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author Masaya Hane
Ayane Naramura
Kaito Hayakawa
Chikara Abe
Takahiro Nakagawa
Itaru Kushima
Soma Furukawa
Yuki Fukami
Keisuke Ikegami
Kazumasa Saigoh
Susumu Kusunoki
Masahisa Katsuno
Norio Ozaki
Ken Kitajima
Chihiro Sato
author_facet Masaya Hane
Ayane Naramura
Kaito Hayakawa
Chikara Abe
Takahiro Nakagawa
Itaru Kushima
Soma Furukawa
Yuki Fukami
Keisuke Ikegami
Kazumasa Saigoh
Susumu Kusunoki
Masahisa Katsuno
Norio Ozaki
Ken Kitajima
Chihiro Sato
author_sort Masaya Hane
collection DOAJ
description Abstract Polysialic acid (polySia), a glycoepitope critical for neural development and plasticity, remains difficult to quantify owing to its structural complexity. Here, we present a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) utilizing novel probes to measure polySia expression. Using this method, we quantified polySia levels in mouse brain samples across various developmental and aging stages. Notable age-related changes were observed, particularly in neuroplastic regions such as the hippocampus and olfactory bulb, where polySia levels increased at 12 months, potentially reflecting resilience mechanisms against brain aging. Elevated polySia levels in blood samples were also detected in both a schizophrenia mouse model and human patients, with a notable male preponderance. In contrast, no significant changes were observed in patients with chronic inflammatory demyelinating polyneuropathy. These findings, enabled by the novel probes, highlight a potential role for polySia in brain aging and neuropsychiatric disorders, offering new insights into developmental and disease mechanisms and supporting its utility as a diagnostic biomarker for brain impairments.
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spelling doaj-art-23e486eb41ae4c6a9b60e8741c0300bd2025-08-20T02:00:00ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-02583-xA highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disordersMasaya Hane0Ayane Naramura1Kaito Hayakawa2Chikara Abe3Takahiro Nakagawa4Itaru Kushima5Soma Furukawa6Yuki Fukami7Keisuke Ikegami8Kazumasa Saigoh9Susumu Kusunoki10Masahisa Katsuno11Norio Ozaki12Ken Kitajima13Chihiro Sato14Integrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya UniversityDepartment of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya UniversityDepartment of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya UniversityIntegrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya UniversityDepartment of Applied Biosciences, Graduate School of Bioagricultural Sciences, Nagoya UniversityDepartment of Psychiatry, Nagoya University Graduate School of MedicineDepartment of Neurology, Nagoya University Graduate School of MedicineDepartment of Neurology, Nagoya University Graduate School of MedicineFaculty of Agriculture, Kyushu UniversityDepartment of Clinical Genetics, Kindai University HospitalDepartment of Neurology, Faculty of Medicine, Kindai UniversityMedical Genomics Center, Nagoya University HospitalIntegrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya UniversityIntegrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya UniversityIntegrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya UniversityAbstract Polysialic acid (polySia), a glycoepitope critical for neural development and plasticity, remains difficult to quantify owing to its structural complexity. Here, we present a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) utilizing novel probes to measure polySia expression. Using this method, we quantified polySia levels in mouse brain samples across various developmental and aging stages. Notable age-related changes were observed, particularly in neuroplastic regions such as the hippocampus and olfactory bulb, where polySia levels increased at 12 months, potentially reflecting resilience mechanisms against brain aging. Elevated polySia levels in blood samples were also detected in both a schizophrenia mouse model and human patients, with a notable male preponderance. In contrast, no significant changes were observed in patients with chronic inflammatory demyelinating polyneuropathy. These findings, enabled by the novel probes, highlight a potential role for polySia in brain aging and neuropsychiatric disorders, offering new insights into developmental and disease mechanisms and supporting its utility as a diagnostic biomarker for brain impairments.https://doi.org/10.1038/s41598-025-02583-x
spellingShingle Masaya Hane
Ayane Naramura
Kaito Hayakawa
Chikara Abe
Takahiro Nakagawa
Itaru Kushima
Soma Furukawa
Yuki Fukami
Keisuke Ikegami
Kazumasa Saigoh
Susumu Kusunoki
Masahisa Katsuno
Norio Ozaki
Ken Kitajima
Chihiro Sato
A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
Scientific Reports
title A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
title_full A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
title_fullStr A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
title_full_unstemmed A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
title_short A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
title_sort highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders
url https://doi.org/10.1038/s41598-025-02583-x
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