Exposure to nonylphenol in early life causes behavioural deficits related with autism spectrum disorders in rats

• Published in: Environment international Vol. 180; p. 108228
• Main Authors: You, Mingdan, Li, Siyao, Yan, Siyu, Yao, Dianqi, Wang, Tingyu, Wang, Yi
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.10.2023; Elsevier
• Subjects: Autism spectrum disorders; Dendritic spine; Endoplasmic reticulum stress; Nonylphenol; Oxidative stress; Oxidative stress; SGT; NP; TCT; E; VPA; PBPK; CNS; MDA; Endoplasmic reticulum stress; EDCs; SC; SD; BSA; ASD; 4-HNE; UPR; TDI; OFT; GSH; MBT; PSD; UV; GSH-Px; SOD; ER; Autism spectrum disorders; mPFC; NOAEL; Dendritic spine; TMT; Nonylphenol; TEM; ATP; PN
• ISSN: 0160-4120; 1873-6750
• DOI: 10.1016/j.envint.2023.108228

[Display omitted] •NP exposure causes behavioral deficits associated with autism spectrum disorders.•ER stress underlies NP-induced dendritic spine loss and synaptic dysfunction.•Damaged mitochondrial function and subsequent oxidative stress account for ER stress.•Dendritic spine loss and synaptic dysfunction might involve in behavioral deficits. 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.