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慢性暴露于传统环境污染物对胼胝体微观结构的影响:对因纽特青少年的扩散 MRI 研究。

Impact of chronic exposure to legacy environmental contaminants on the corpus callosum microstructure: A diffusion MRI study of Inuit adolescents.

机构信息

Department of Psychology, Université du Québec à Montréal, Montréal, Québec, Canada; Sainte-Justine University Hospital Research Center, Montréal, Québec, Canada.

School of Psychology, Université Laval, Québec, Québec, Canada; Centre de Recherche du CHUQ de Québec, Université Laval, Québec, Canada.

出版信息

Neurotoxicology. 2022 Sep;92:200-211. doi: 10.1016/j.neuro.2022.08.010. Epub 2022 Aug 20.

DOI:10.1016/j.neuro.2022.08.010
PMID:35995272
Abstract

Exposure to environmental contaminants is an important public health concern for the Inuit population of northern Québec, who have been exposed to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb). During the last 25 years, the Nunavik Child Development Study (NCDS) birth cohort has reported adverse associations between these exposures and brain function outcomes. In the current study, we aimed to determine whether contaminant exposure is associated with alterations of the corpus callosum (CC), which plays an important role in various cognitive, motor and sensory function processes. Magnetic resonance imaging (MRI) was administered to 89 NCDS participants (mean age ± SD = 18.4 ± 1.2). Diffusion-weighted imaging was assessed to characterize the microstructure of the CC white matter in 7 structurally and functionally distinct regions of interest (ROIs) using a tractography-based segmentation approach. The following metrics were computed: fiber tract density, fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Multiple linear regression models adjusted for sex, age, current alcohol/drug use and fish nutrients (omega-3 fatty acids and selenium) were conducted to assess the association between diffusion-weighted imaging metrics and Hg, PCB 153 and Pb concentrations obtained at birth in the cord blood and postnatally (mean values from blood samples at 11 and 18 years of age). Exposures were not associated with fiber tract density. Nor were significant associations found with cord and postnatal blood Pb concentrations for FA. However, pre- and postnatal Hg and PCB concentrations were significantly associated with higher FA of several regions of the CC, namely anterior midbody, posterior midbody, isthmus, and splenium, with the most pronounced effects observed in the splenium. FA results were mainly associated with lower RD. This study shows that exposure to Hg and PCB 153 alters the posterior microstructure of the CC, providing neuroimaging evidence of how developmental exposure to environmental chemicals can impair brain function and behavior in late adolescence.

摘要

接触环境污染物是北极魁北克因纽特人(Inuit)群体面临的一个重要公共卫生问题,他们接触过汞(Hg)、多氯联苯(PCBs)和铅(Pb)。在过去的 25 年中,努纳维克儿童发展研究(Nunavik Child Development Study,NCDS)出生队列报告了这些暴露与大脑功能结果之间的不良关联。在当前的研究中,我们旨在确定污染物暴露是否与胼胝体(corpus callosum,CC)的改变有关,CC 在各种认知、运动和感觉功能过程中起着重要作用。对 89 名 NCDS 参与者(平均年龄 ± 标准差 = 18.4 ± 1.2 岁)进行了磁共振成像(Magnetic Resonance Imaging,MRI)检查。使用基于束追踪的分割方法,对 7 个结构和功能不同的感兴趣区(region of interest,ROI)中的 CC 白质进行弥散加权成像(diffusion-weighted imaging,DWI)评估,以表征 CC 白质的微观结构。计算了以下指标:纤维束密度、各向异性分数(fractional anisotropy,FA)、轴向弥散度(axial diffusivity,AD)和径向弥散度(radial diffusivity,RD)。进行了多元线性回归模型分析,调整了性别、年龄、当前的酒精/药物使用情况以及鱼类营养物质(ω-3 脂肪酸和硒),以评估 DWI 指标与出生时脐带血和出生后(11 岁和 18 岁时的血液样本平均值)中 Hg、PCB153 和 Pb 浓度之间的关联。暴露与纤维束密度无关。FA 与脐带血和出生后血 Pb 浓度之间也没有显著关联。然而,Hg 和 PCB153 的产前和产后浓度与 CC 的几个区域的 FA 呈显著正相关,特别是胼胝体的前体中部、后体中部、峡部和压部,其中在压部观察到的影响最为显著。FA 结果主要与 RD 降低有关。这项研究表明,Hg 和 PCB153 的暴露会改变 CC 的后部微观结构,为环境化学物质对大脑的发育暴露如何损害青春期后期的大脑功能和行为提供了神经影像学证据。

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