Air pollution decreases postsynaptic PSD-95 and NMDA receptor subunits in synaptosomes from mouse cerebral cortex

IF 7.6 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Pollution Pub Date : 2025-07-17 DOI:10.1016/j.envpol.2025.126845

Jose A. Godoy-Lugo , Daniel Hicks , Salma Durra , Emma R. Massey , Kristina Shkirkova , Ariel I. Sauri , Elizabeth Kerstiens , Selena Chen , Lifu Zhao , Constantinos Sioutas , William J. Mack , Caleb E. Finch , Max A. Thorwald

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Abstract

Air pollution (AirP) increases the risk of accelerated cognitive decline, dementia, and behavioral disorders associated with oxidative damage in humans. These AirP responses are shared with rodent models. The underlying impact of AirP-mediated molecular changes on synapses remains unexplored. We examined synaptosomes extracted from cerebral cortex of mice chronically exposed to inhaled diesel exhaust particles (DEP) for 8 weeks. DEP selectively decreased postsynaptic proteins (PSD-95; p = 0.04, SAP97; p = 0.01) by at least 20 % and NMDA receptor subunits (GluN1; p = 0.03, N2A; p = 0.009, N2B; p = 0.01) by 15 %, without altering the evaluated pre-synaptic proteins. Antioxidant enzymes for oxidized phospholipid repair (GPx4; p = 0.015), iron metabolism (HMOX1; p = 0.04), and glutathione synthesis (GCLC; p = 0.008), which participate in mitigating ferroptosis, a form of cell death present in Alzheimer's disease, increased by at least 15 %. These findings suggest subcellular responses to AirP in glutamatergic synapses. Further analyses of the impact of AirP on synapses may consider protective mechanisms by antioxidant enzymes to enhance cognitive health at all ages.

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空气污染降低小鼠大脑皮层突触小体突触后PSD-95和NMDA受体亚基

空气污染（AirP）增加了人类与氧化损伤相关的认知能力加速下降、痴呆和行为障碍的风险。这些AirP反应与啮齿动物模型相同。airp介导的分子变化对突触的潜在影响尚不清楚。我们检测了从长期暴露于吸入柴油废气颗粒（DEP） 8周的小鼠大脑皮层提取的突触体。DEP选择性地降低了至少20%的突触后蛋白（PSD-95, p=0.04, SAP97, p=0.01）和15%的NMDA受体亚基（GluN1, p=0.03, N2A, p=0.009, N2B, p=0.01），而未改变评估的突触前蛋白。抗氧化酶用于氧化磷脂修复（GPx4, p=0.015）、铁代谢（HMOX1, p=0.04）和谷胱甘肽合成(GCLC；p=0.008)，它们参与减轻铁下垂（阿尔茨海默病中存在的一种细胞死亡形式），至少增加了15%。这些发现提示在谷氨酸突触中对AirP有亚细胞反应。进一步分析AirP对突触的影响可能会考虑抗氧化酶的保护机制，以增强所有年龄段的认知健康。

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来源期刊

Environmental Pollution 环境科学-环境科学

CiteScore

16.00

自引率

6.70%

发文量

2082

审稿时长

2.9 months

期刊介绍： Environmental Pollution is an international peer-reviewed journal that publishes high-quality research papers and review articles covering all aspects of environmental pollution and its impacts on ecosystems and human health. Subject areas include, but are not limited to: • Sources and occurrences of pollutants that are clearly defined and measured in environmental compartments, food and food-related items, and human bodies; • Interlinks between contaminant exposure and biological, ecological, and human health effects, including those of climate change; • Contaminants of emerging concerns (including but not limited to antibiotic resistant microorganisms or genes, microplastics/nanoplastics, electronic wastes, light, and noise) and/or their biological, ecological, or human health effects; • Laboratory and field studies on the remediation/mitigation of environmental pollution via new techniques and with clear links to biological, ecological, or human health effects; • Modeling of pollution processes, patterns, or trends that is of clear environmental and/or human health interest; • New techniques that measure and examine environmental occurrences, transport, behavior, and effects of pollutants within the environment or the laboratory, provided that they can be clearly used to address problems within regional or global environmental compartments.