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Published on: April 26, 2018
Single-nucleus transcriptomics reveals cell-type-resolved brain responses to concurrent exposure to polyethylene
Yitong Lu1, Houdao Ren1, Zhongting Lv1
1College of Food Science and Engineering, Jilin University, Changchun 130062, China.
Abstract:
The co-occurrence of plastic-derived particles and plastic-associated chemicals represents an emerging toxicological concern, yet their combined neurotoxicity remains insufficiently understood. Here, we evaluated whether repeated oral concurrent exposure to polyethylene nanoplastics (PE-NPs) and butyl benzyl phthalate (BBP) aggravates neurotoxic outcomes and characterized associated cell-type-resolved brain responses. In HT-22 neuronal cells, concentration-response matrix analysis revealed a positive interaction pattern between PE-NPs and BBP. A 90-day oral exposure model was then established in mice using pristine 50 nm PE-NPs, BBP, and their combination. Compared with single exposures, concurrent exposure caused more pronounced impairment in locomotor/exploratory behavior and spatial learning, accompanied by aggravated hippocampal neuronal and synaptic injury, neurotransmitter disturbance, enhanced glial reactivity, and reduced tight-junction-associated markers. Whole-brain single-nucleus RNA sequencing of control and co-exposure groups identified co-exposure-associated transcriptional alterations across neuronal, glial, and endothelial populations, involving synaptic organization, mitochondrial bioenergetics, glial/complement responses, and neurovascular barrier-related processes. Cell-cell communication analysis further suggested contraction of neuronal adhesion/trophic and vascular-associated signaling networks under the co-exposure condition. Targeted qRT-PCR validation using all four exposure groups supported representative snRNA-seq-derived candidates, including decreased Rbfox3, Rims1, Erbb4, Nrg1, Ptprm, and Cldn5 and increased Apoe and C1qa, with significant PE-NP × BBP interactions detected for Apoe, C1qa, and Cldn5. Overall, these findings show that concurrent PE-NP and BBP exposure aggravated neurotoxic outcomes and highlight the need to consider mixed plastic-derived contaminants in neurotoxicity assessment.
