产前和童年时期的空气污染暴露、细胞免疫生物标志物以及青少年早期的大脑连通性

IF 3.7 Q2 IMMUNOLOGY
Devyn L. Cotter , Jessica Morrel , Kirthana Sukumaran , Carlos Cardenas-Iniguez , Joel Schwartz , Megan M. Herting
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引用次数: 0

摘要

导言:环境空气污染是一种神经毒剂,其假设机制与免疫有关。青少年的大脑结构和功能连通性可能特别容易受到环境污染的影响,因为这一时期大规模大脑网络的完善程度因性别而异,并对认知、行为和情感功能产生重要影响。在本研究中,我们利用青少年大脑认知发展℠研究®的横断面性别分层数据,探讨了空气污染物、免疫标记物与青春期早期的结构和功能连接性之间的关联。方法采用基于集合的建模方法,将细颗粒物、二氧化氮和臭氧的污染物浓度分配到每个孩子在产前和儿童期(9-10 岁)的主要居住地址。11-13 岁时收集的数据包括默认模式、额顶叶、显著性网络和边缘相关区域的静息状态功能连接、可用白质束的细胞内定向和各向同性扩散以及细胞免疫激活标记。利用偏最小二乘法相关性(一种多变量数据驱动方法,可识别潜在维度中的重要变量),我们研究了1)污染物与结构和功能连通性之间的关联;2)污染物与免疫标记物之间的关联;3)免疫标记物与结构和功能连通性之间的关联。11-13岁时,污染物与静息态功能连通性之间没有关联。儿童期接触二氧化氮与男性白细胞计数呈负相关。女性的免疫生物标志物与白质细胞内定向扩散呈正相关,而男性的白质细胞内定向扩散和各向同性扩散均呈正相关。最后,在女性中,淋巴细胞与单核细胞比率与默认模式网络静息状态功能连通性之间存在可靠的负相关;在男性中,免疫标志物特征受损与显著性网络和左侧海马之间较低的静息状态功能连通性有关。在事后探索性分析中,我们发现 PLSC 确定的白质束和静息状态网络与 NIH 工具箱中的处理速度和认知控制表现有关。未来的研究应探索免疫活动在污染物如何影响神经系统结果方面的潜在中介作用,以及与免疫相关的大脑连接模式在改善所有人大脑健康方面的潜在后果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents

Introduction

Ambient air pollution is a neurotoxicant with hypothesized immune-related mechanisms. Adolescent brain structural and functional connectivity may be especially vulnerable to ambient pollution due to the refinement of large-scale brain networks during this period, which vary by sex and have important implications for cognitive, behavioral, and emotional functioning. In the current study we explored associations between air pollutants, immune markers, and structural and functional connectivity in early adolescence by leveraging cross-sectional sex-stratified data from the Adolescent Brain Cognitive Development℠ Study®.

Methods

Pollutant concentrations of fine particulate matter, nitrogen dioxide, and ozone were assigned to each child's primary residential address during the prenatal period and childhood (9-10 years-old) using an ensemble-based modeling approach. Data collected at 11-13 years-old included resting-state functional connectivity of the default mode, frontoparietal, and salience networks and limbic regions of interest, intracellular directional and isotropic diffusion of available white matter tracts, and markers of cellular immune activation. Using partial least squares correlation, a multivariate data-driven method that identifies important variables within latent dimensions, we investigated associations between 1) pollutants and structural and functional connectivity, 2) pollutants and immune markers, and 3) immune markers and structural and functional connectivity, in each sex separately.

Results

Air pollution exposure was related to white matter intracellular directional and isotropic diffusion at ages 11–13 years, but the direction of associations varied by sex. There were no associations between pollutants and resting-state functional connectivity at ages 11–13 years. Childhood exposure to nitrogen dioxide was negatively correlated with white blood cell count in males. Immune biomarkers were positively correlated with white matter intracellular directional diffusion in females and both white matter intracellular directional and isotropic diffusion in males. Lastly, there was a reliable negative correlation between lymphocyte-to-monocyte ratio and default mode network resting-state functional connectivity in females, as well as a compromised immune marker profile associated with lower resting-state functional connectivity between the salience network and the left hippocampus in males. In post-hoc exploratory analyses, we found that the PLSC-identified white matter tracts and resting-state networks related to processing speed and cognitive control performance from the NIH Toolbox.

Conclusions

We identified novel links between childhood nitrogen dioxide and cellular immune activation in males, and brain network connectivity and immune markers in both sexes. Future research should explore the potentially mediating role of immune activity in how pollutants affect neurological outcomes as well as the potential consequences of immune-related patterns of brain connectivity in service of improved brain health for all.

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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
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97 days
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