Identification of ceRNA network to explain the mechanism of cognitive dysfunctions induced by PS NPs in mice

Abstract

Plastics breaking down of larger plastics into smaller ones (microplastics and nanoplastic) as potential threats to the ecosystem. Previous studies demonstrate that the central nervous system (CNS) is a vulnerable target of nanoplastics. However, the potentially epigenetic biomarkers of nanoplastic neurotoxicity in rodent models are still unknown. The present research aimed to determine the role of competing endogenous RNA (ceRNA) in the process of polystyrene nanoplastics (PS NPs) exposure-induced nerve injury. The study was designed to investigate whether 25 nm PS NPs could cause learning dysfunction and to elucidate the underlying mechanisms in mice. A total of 40 mice were divided into 4 groups and were exposed to PS NPs (0, 10, 25, 50 mg/kg). Chronic toxicity was introduced in mice by administration of oral gavage for 6 months. The evaluation included assessment of their behavior, pathological investigation and determination of the levels of reactive oxygen species (ROS) and DNA damage. RNA-Seq was performed to detect the expression levels of circRNAs, miRNAs and mRNAs in PFC samples of mice treated with 0 and 50 mg/kg PS NPs. The results indicated that exposure of mice to PS NPs caused a dose-dependent cognitive decline. ROS levels and DNA damage were increased in the PFC following exposure of the mice to PS NPs. A total of 987 mRNAs, 29 miRNAs and 67 circRNAs demonstrated significant differences between the 0 and 50 mg/kg PS NPs groups. Functional enrichment analyses indicated that PS NPs may induce major injury in the synaptic function. A total of 96 mRNAs, which were associated with synaptic dysfunction were identified. A competing endogenous RNA (ceRNA) network containing 27 circRNAs, 19 miRNAs and 35 synaptic dysfunction-related mRNAs was constructed. The present study provided insight into the molecular events associated with nanoplastic toxicity and induction of cognitive dysfunction.

Keywords: Cognitive decline; Nano-polystyrene; RNA sequencing; Synaptic dysfunction; ceRNA.