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自闭症患者大脑额区和枕区的谷胱甘肽水平没有变化。

Frontal and occipital brain glutathione levels are unchanged in autistic adults.

机构信息

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Portugal, Coimbra, Portugal.

出版信息

PLoS One. 2024 Aug 15;19(8):e0308792. doi: 10.1371/journal.pone.0308792. eCollection 2024.

Abstract

BACKGROUND

The neurobiological underpinnings of Autism Spectrum Disorder (ASD) are diverse and likely multifactorial. One possible mechanism is increased oxidative stress leading to altered neurodevelopment and brain function. However, this hypothesis has mostly been tested in post-mortem studies. So far, available in vivo studies in autistic individuals have reported no differences in glutathione (GSH) levels in frontal, occipital, and subcortical regions. However, these studies were limited by the technically challenging quantification of GSH, the main brain antioxidant molecule. This study aimed to overcome previous studies' limitations by using a GSH-tailored spectroscopy sequence and optimised quantification methodology to provide clarity on GSH levels in autistic adults.

METHODS

We used spectral editing proton-magnetic resonance spectroscopy (1H-MRS) combined with linear combination model fitting to quantify GSH in the dorsomedial prefrontal cortex (DMPFC) and medial occipital cortex (mOCC) of autistic and non-autistic adults (male and female). We compared GSH levels between groups. We also examined correlations between GSH and current autism symptoms, measured using the Autism Quotient (AQ).

RESULTS

Data were available from 31 adult autistic participants (24 males, 7 females) and 40 non-autistic participants (21 males, 16 females); the largest sample to date. The GSH levels did not differ between groups in either region. No correlations with AQ were observed.

CONCLUSION

GSH levels as measured using 1H-MRS are unaltered in the DMPFC and mOCC regions of autistic adults, suggesting that oxidative stress in these cortical regions is not a marked neurobiological signature of ASD.

摘要

背景

自闭症谱系障碍(ASD)的神经生物学基础是多样的,可能是多因素的。一种可能的机制是氧化应激增加,导致神经发育和大脑功能改变。然而,这一假设主要是在尸检研究中进行测试的。到目前为止,在自闭症个体中进行的现有活体研究报告称,额、枕和皮质下区域的谷胱甘肽(GSH)水平没有差异。然而,这些研究受到技术上具有挑战性的 GSH 定量的限制,GSH 是大脑主要的抗氧化分子。本研究旨在通过使用 GSH 定制的光谱序列和优化的定量方法来克服以前研究的局限性,以明确自闭症成人的 GSH 水平。

方法

我们使用谱编辑质子磁共振波谱(1H-MRS)结合线性组合模型拟合来定量自闭症和非自闭症成人(男性和女性)的背内侧前额叶皮层(DMPFC)和内侧枕叶皮层(mOCC)中的 GSH。我们比较了两组之间的 GSH 水平。我们还检查了 GSH 与当前自闭症症状之间的相关性,使用自闭症量表(AQ)进行测量。

结果

数据来自 31 名成年自闭症患者(24 名男性,7 名女性)和 40 名非自闭症患者(21 名男性,16 名女性);这是迄今为止最大的样本量。两组在两个区域的 GSH 水平均无差异。未观察到与 AQ 的相关性。

结论

使用 1H-MRS 测量的 GSH 水平在自闭症成人的 DMPFC 和 mOCC 区域没有改变,这表明这些皮质区域的氧化应激不是 ASD 的明显神经生物学特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b47a/11326623/4f0dbef7ff2f/pone.0308792.g001.jpg

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