Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis
Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024001090 |
| _version_ | 1797248443254571008 |
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| author | Ji Wang Ying Yang Yongpeng Shi Li Wei Lan Gao Mingxin Liu |
| author_facet | Ji Wang Ying Yang Yongpeng Shi Li Wei Lan Gao Mingxin Liu |
| author_sort | Ji Wang |
| collection | DOAJ |
| description | Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox-LDPE) and established a model of MPs exposure by continuously orally gavage of C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days with or without oral administration of Lactobacillus plantarum DP189 and galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs or Ox-LDPE-MPs caused several adverse effects in mice, mainly manifested by behavioral changes, disruption of the intestinal and blood–brain barrier (BBB), and simultaneous oxidative stress, inflammatory reactions, and pathological damage in the brain and intestines. Brain transcriptomic analysis revealed that the cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after exposure to LDPE-MPs or Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction and Western Blotting results further demonstrated that the critical genes (Slc5a7, Chat and Slc18a3) and proteins (Chat and Slc18a3) in the cholinergic synaptic signaling pathway were significantly down-regulated after exposure to LDPE-MPs or Ox-LDPE-MPs. These alterations lead to reduced acetylcholine concentration, which causes cognitive dysfunction in mice. Importantly, the DP189&GOS interventions effectively mitigated the MPs-induced cognitive dysfunction and intestinal microbiota alteration, improved intestinal and BBB integrity, attenuated the oxidative stress and inflammatory response, and also saw a rebound in the release of acetylcholine. These results indicated that LDPE-MPs and Ox-LDPE-MPs exert neurotoxic effects on mice by inducing oxidative stress, inflammatory responses, and dysregulation of cholinergic signaling pathways in the mouse brain. That probiotic supplementation is effective in attenuating MPs-induced neurotoxicity in mice. Overall, this study reveals the potential mechanisms of neurotoxicity of LDPE-MPs and Ox-LDPE-MPs on mice and their improvement measures, necessary to assess the potential risks of plastic contaminants to human health. |
| first_indexed | 2024-04-24T20:14:40Z |
| format | Article |
| id | doaj.art-d094c0e3354f4eee87acfde966284235 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T20:14:40Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-d094c0e3354f4eee87acfde9662842352024-03-23T06:22:10ZengElsevierEnvironment International0160-41202024-03-01185108523Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axisJi Wang0Ying Yang1Yongpeng Shi2Li Wei3Lan Gao4Mingxin Liu5School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, ChinaSchool of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, ChinaSchool of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, ChinaSchool of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, ChinaSchool of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, China; Corresponding authors.State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, No. 222 South Tianshui Road, Lanzhou 730000, Gansu Province, China; Corresponding authors.Microplastics (MPs) are inevitably oxidized in the environment, and their potential toxicity to organisms has attracted wide attention. However, the neurotoxicity and mechanism of oxidized polyethylene (Ox-PE) MPs to organisms remain unclear. Herein, we prepared oxidized low-density polyethylene (Ox-LDPE) and established a model of MPs exposure by continuously orally gavage of C57BL/6 J mice with LDPE-MPs/Ox-LDPE-MPs for 28 days with or without oral administration of Lactobacillus plantarum DP189 and galactooligosaccharides (DP189&GOS). The experimental results indicated that LDPE-MPs or Ox-LDPE-MPs caused several adverse effects in mice, mainly manifested by behavioral changes, disruption of the intestinal and blood–brain barrier (BBB), and simultaneous oxidative stress, inflammatory reactions, and pathological damage in the brain and intestines. Brain transcriptomic analysis revealed that the cholinergic synaptic signaling pathways, which affect cognitive function, were significantly disrupted after exposure to LDPE-MPs or Ox-LDPE-MPs. Real-time quantitative polymerase chain reaction and Western Blotting results further demonstrated that the critical genes (Slc5a7, Chat and Slc18a3) and proteins (Chat and Slc18a3) in the cholinergic synaptic signaling pathway were significantly down-regulated after exposure to LDPE-MPs or Ox-LDPE-MPs. These alterations lead to reduced acetylcholine concentration, which causes cognitive dysfunction in mice. Importantly, the DP189&GOS interventions effectively mitigated the MPs-induced cognitive dysfunction and intestinal microbiota alteration, improved intestinal and BBB integrity, attenuated the oxidative stress and inflammatory response, and also saw a rebound in the release of acetylcholine. These results indicated that LDPE-MPs and Ox-LDPE-MPs exert neurotoxic effects on mice by inducing oxidative stress, inflammatory responses, and dysregulation of cholinergic signaling pathways in the mouse brain. That probiotic supplementation is effective in attenuating MPs-induced neurotoxicity in mice. Overall, this study reveals the potential mechanisms of neurotoxicity of LDPE-MPs and Ox-LDPE-MPs on mice and their improvement measures, necessary to assess the potential risks of plastic contaminants to human health.http://www.sciencedirect.com/science/article/pii/S0160412024001090Low-density polyethylene microplasticsOxidized low-density polyethylene microplasticsMicrobiota-gut-brain axisCholinergic systemLactobacillus plantarum DP189Mice |
| spellingShingle | Ji Wang Ying Yang Yongpeng Shi Li Wei Lan Gao Mingxin Liu Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis Environment International Low-density polyethylene microplastics Oxidized low-density polyethylene microplastics Microbiota-gut-brain axis Cholinergic system Lactobacillus plantarum DP189 Mice |
| title | Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis |
| title_full | Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis |
| title_fullStr | Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis |
| title_full_unstemmed | Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis |
| title_short | Oxidized/unmodified-polyethylene microplastics neurotoxicity in mice: Perspective from microbiota-gut-brain axis |
| title_sort | oxidized unmodified polyethylene microplastics neurotoxicity in mice perspective from microbiota gut brain axis |
| topic | Low-density polyethylene microplastics Oxidized low-density polyethylene microplastics Microbiota-gut-brain axis Cholinergic system Lactobacillus plantarum DP189 Mice |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024001090 |
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