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多模态脑白质成像显示精神分裂症患者羰基应激增强与表观轴突密度降低有关。

Association between enhanced carbonyl stress and decreased apparent axonal density in schizophrenia by multimodal white matter imaging.

机构信息

Department of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-Ku, Kyoto, 606-8507, Japan.

Project for Schizophrenia Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

出版信息

Sci Rep. 2023 Jul 27;13(1):12220. doi: 10.1038/s41598-023-39379-w.

DOI:10.1038/s41598-023-39379-w
PMID:37500709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10374594/
Abstract

Carbonyl stress is a condition featuring increased rich reactive carbonyl compounds, which facilitate the formation of advanced glycation end products including pentosidine. We previously reported the relationship between enhanced carbonyl stress and disrupted white matter integrity in schizophrenia, although which microstructural component is disrupted remained unclear. In this study, 32 patients with schizophrenia (SCZ) and 45 age- and gender-matched healthy volunteers (HC) were recruited. We obtained blood samples for carbonyl stress markers (plasma pentosidine and serum pyridoxal) and multi-modal magnetic resonance imaging measures of white matter microstructures including apparent axonal density (intra-cellular volume fraction (ICVF)) and orientation (orientation dispersion index (ODI)), and inflammation (free water (FW)). In SCZ, the plasma pentosidine level was significantly increased. Group comparison revealed that mean white matter values were decreased for ICVF, and increased for FW. We found a significant negative correlation between the plasma pentosidine level and mean ICVF values in SCZ, and a significant negative correlation between the serum pyridoxal level and mean ODI value in HC, regardless of age. Our results suggest an association between enhanced carbonyl stress and axonal abnormality in SCZ.

摘要

羰基应激是一种特征为富含反应性羰基化合物增加的状态，这有助于形成晚期糖基化终产物，包括戊糖素。我们之前报道了增强的羰基应激与精神分裂症患者的白质完整性破坏之间的关系，尽管破坏的是哪个微观结构成分尚不清楚。在这项研究中，我们招募了 32 名精神分裂症患者（SCZ）和 45 名年龄和性别匹配的健康志愿者（HC）。我们获得了血液样本以测量羰基应激标志物（血浆戊糖素和血清吡哆醛）和白质微观结构的多模态磁共振成像测量值，包括明显的轴突密度（细胞内体积分数（ICVF））和方向（方向分散指数（ODI）），以及炎症（游离水（FW））。在 SCZ 中，血浆戊糖素水平显著升高。组间比较显示，SCZ 的平均白质值 ICVF 降低，FW 增加。我们发现，SCZ 中血浆戊糖素水平与平均 ICVF 值呈显著负相关，HC 中血清吡哆醛水平与平均 ODI 值呈显著负相关，而与年龄无关。我们的结果表明，增强的羰基应激与 SCZ 中的轴突异常之间存在关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/7109581d75c9/41598_2023_39379_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/8456cba20f85/41598_2023_39379_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/15d585626415/41598_2023_39379_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/39b762fc61e1/41598_2023_39379_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/7109581d75c9/41598_2023_39379_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/8456cba20f85/41598_2023_39379_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/15d585626415/41598_2023_39379_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/39b762fc61e1/41598_2023_39379_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db86/10374594/7109581d75c9/41598_2023_39379_Fig4_HTML.jpg

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本文引用的文献

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Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex.联合糖氧还蛋白 1 功能障碍和维生素 B6 缺乏在精神分裂症模型系统中导致前额叶皮层线粒体功能障碍。
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Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures.精神分裂症病例和对照的脑毛细血管结构与其神经元结构相关。
Sci Rep. 2021 Jun 3;11(1):11768. doi: 10.1038/s41598-021-91233-z.
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Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons.
一氧甲酰酶 I 的缺失和细胞外羰基应激会损害人诱导多能干细胞及其衍生神经元中的线粒体功能。
Transl Psychiatry. 2021 May 8;11(1):275. doi: 10.1038/s41398-021-01392-w.
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Structural diverseness of neurons between brain areas and between cases.脑区之间和病例之间神经元的结构多样性。
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Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals.大样本证据表明精神分裂症患者和健康个体外周炎症与脑白质自由水相关。
Schizophr Bull. 2021 Mar 16;47(2):542-551. doi: 10.1093/schbul/sbaa134.
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The accumulation of advanced glycation end-products in a schizophrenic patient with a glyoxalase 1 frameshift mutation: An autopsy study.一名患有乙二醛酶1移码突变的精神分裂症患者体内晚期糖基化终产物的积累：一项尸检研究。
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