Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China; School of Public Heath, Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China; Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People's Republic of China.
Environ Int. 2023 Oct;180:108228. doi: 10.1016/j.envint.2023.108228. Epub 2023 Sep 27.
Early-life exposure to environmental endocrine disruptors (EDCs) is a potential risk factor for autism spectrum disorder (ASD). Exposure to nonylphenol (NP), a typical EDC, is known to cause some long-term behavioural abnormalities. Moreover, these abnormal behaviours are the most frequent psychiatric co-morbidities in ASD. However, the direct evidence for the link between NP exposure in early life and ASD-like behavioural phenotypes is still missing. In the present study, typical ASD-like behaviours induced by valproic acid treatment were considered as a positive behavioural control. We investigated impacts on social behaviours following early-life exposure to NP, and explored effects of this exposure on neuronal dendritic spines, mitochondria function, oxidative stress, and endoplasmic reticulum (ER) stress. Furthermore, primary cultured rat neurons were employed as in vitro model to evaluate changes in dendritic spine caused by exposure to NP, and oxidative stress and ER stress were specifically modulated to further explore their roles in these changes. Our results indicated rats exposed to NP in early life showed mild ASD-like behaviours. Moreover, we also found the activation of ER stress triggered by oxidative stress may contribute to dendritic spine decrease and synaptic dysfunction, which may underlie neurobehavioural abnormalities induced by early-life exposure to NP.
早期生活环境内分泌干扰物（EDCs）暴露是自闭症谱系障碍（ASD）的一个潜在风险因素。暴露于壬基酚（NP），一种典型的 EDC，已知会导致一些长期的行为异常。此外，这些异常行为是 ASD 中最常见的精神共病。然而，NP 早期暴露与 ASD 样行为表型之间的联系的直接证据仍然缺乏。在本研究中，丙戊酸治疗引起的典型 ASD 样行为被认为是一种阳性行为对照。我们研究了早期 NP 暴露对社会行为的影响，并探讨了这种暴露对神经元树突棘、线粒体功能、氧化应激和内质网（ER）应激的影响。此外，我们还使用原代培养的大鼠神经元作为体外模型，评估 NP 暴露引起的树突棘变化，并特异性调节氧化应激和 ER 应激，以进一步探讨它们在这些变化中的作用。我们的结果表明，早期生活中暴露于 NP 的大鼠表现出轻微的 ASD 样行为。此外，我们还发现氧化应激引发的 ER 应激激活可能导致树突棘减少和突触功能障碍，这可能是 NP 早期暴露引起神经行为异常的基础。
