Early clues and molecular mechanism involved in neurodegenerative diseases induced in immature mice by combined exposure to polypropylene microplastics and DEHP

Ge Yang; Cunyi Gong; Xinyue Zheng; Fei Hu; Jie Liu; Tian Wang; Xinyue Chen; Min Li; Zhihong Zhu; Ling Zhang; Rui Li

doi:10.1016/j.envpol.2023.122406

Early clues and molecular mechanism involved in neurodegenerative diseases induced in immature mice by combined exposure to polypropylene microplastics and DEHP

Environ Pollut. 2023 Nov 1:336:122406. doi: 10.1016/j.envpol.2023.122406. Epub 2023 Aug 17.

Authors

Ge Yang¹, Cunyi Gong¹, Xinyue Zheng¹, Fei Hu¹, Jie Liu², Tian Wang³, Xinyue Chen¹, Min Li¹, Zhihong Zhu⁴, Ling Zhang⁵, Rui Li⁶

Affiliations

¹ Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China.
² Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China; The Primary School Attached to Central China Normal University, Wuhan, 430079, China.
³ Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China; College of Civil Engineering, Huaqiao University, Xiamen, 361021, China.
⁴ Institute of Nanoscience and Nanotechnology, College of Physical Science and Technology, Central China Normal University, Wuhan, 430079, China.
⁵ School of Public Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan, 430065, China.
⁶ Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China. Electronic address: ruili@ccnu.edu.cn.

PMID: 37597731
DOI: 10.1016/j.envpol.2023.122406

Abstract

Studies have shown that exposure to either microplastics (MPs) or di-(2-ethylhexyl) phthalic acid (DEHP) alone can cause neurotoxicity in animals, but it remains uncertain whether and to what extent co-exposure to these two substances, which often occur together in reality, can also induce neurotoxicity. This study aimed to investigate the neurotoxicity and molecular mechanisms of combined exposure to DEHP and polypropylene microplastics (synthetic PP-MPs were used), the microplastics most commonly encountered by young children, in immature mice. The results showed that exposure to PP-MPs and/or DEHP did cause neurotoxic effects in immature mice, including induction of neurocognitive and memory deficits, damage to the CA3 region of the hippocampus, increased oxidative stress, and decreased AChE activity in the brain. The severity of the neurotoxicity increased with increasing concentrations of PP-MPs, combined exposure to PP-MPs and DEHP exhibited additive or synergistic effects. Transcriptomic analyses revealed that the PP-MPs and/or DEHP exposure altered the expression profiles of gene clusters involved in the stress response, and in protein processing in endoplasmic reticulum. Quantitative analyses further indicated that PP-MPs and/or DEHP exposure inhibited the activity of the heat shock response mediated by heat shock transcription factor 1, while chronically activated the unfolded protein response, consequently inducing neurotoxicity through neuronal apoptosis and neuroinflammation in the immature mice. As a pioneer study to highlight the neurotoxicity induced by combined exposure to PP-MPs and DEHP in immature mice, this research provides new insights into mitigating the health risks of PP-MPs and DEHP exposure in young children.

Keywords: Combined effect; DEHP; Heat shock response; Immature mice; Neurotoxicity; Polypropylene microplastics.