Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking
Abstract Evidence suggests that early life exposure to Bisphenol A (BPA) may impact neurobehavioral development in animals. BPA has been linked to changes in the dopamine level in the brain. However, molecular and cellular details of how BPA exposure causes these behavioral and cognitive outcomes ar...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-98084-y |
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| author | Yu Shi Xiaoye Feng Chang Y. Chung |
| author_facet | Yu Shi Xiaoye Feng Chang Y. Chung |
| author_sort | Yu Shi |
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| description | Abstract Evidence suggests that early life exposure to Bisphenol A (BPA) may impact neurobehavioral development in animals. BPA has been linked to changes in the dopamine level in the brain. However, molecular and cellular details of how BPA exposure causes these behavioral and cognitive outcomes are poorly understood. We examined how BPA affects the behaviors of adult mice and found that BPA induced hyperactivity and abnormal reward feedback in mice exposed at the early adult stage. We hypothesized that BPA might cause hyperactivity in mice by suppressing DAT trafficking. Fluorescence microscopy revealed that YFP-DAT remains in the perinuclear area when treated with BPA, compared to broader distribution throughout the cytoplasm in control cells. Results from MPTP toxicity and APP + uptake assays indicate that the surface expression of DAT was reduced by BPA treatment. Immunofluorescence staining of neurons in the Substantia nigra (SN) area of the mouse brain also revealed that DAT remains in the perinuclear region, indicating lower surface expression of DAT in the SN, playing important roles in reward and movement. We used another in vivo model, C. elegans, expressing GFP-tagged DAT-1 fusion protein and found that exposure to 50 µM BPA induced a significant increase in the frequency of body bends. However, the frequency of body bends was significantly reduced at 100 µM BPA, indicating biphasic effects of BPA. In conclusion, our results suggest that BPA contributes to the alterations of mice and worm behavior by reducing DAT expression on the surface of neurons via blocking of DAT trafficking. |
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| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-bfbd173cd5314378abe5c5637ac6752c2025-08-20T02:17:54ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-98084-yChronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter traffickingYu Shi0Xiaoye Feng1Chang Y. Chung2School of Pharmaceutical Science and Technology, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Tianjin UniversitySchool of Pharmaceutical Science and Technology, Tianjin UniversityAbstract Evidence suggests that early life exposure to Bisphenol A (BPA) may impact neurobehavioral development in animals. BPA has been linked to changes in the dopamine level in the brain. However, molecular and cellular details of how BPA exposure causes these behavioral and cognitive outcomes are poorly understood. We examined how BPA affects the behaviors of adult mice and found that BPA induced hyperactivity and abnormal reward feedback in mice exposed at the early adult stage. We hypothesized that BPA might cause hyperactivity in mice by suppressing DAT trafficking. Fluorescence microscopy revealed that YFP-DAT remains in the perinuclear area when treated with BPA, compared to broader distribution throughout the cytoplasm in control cells. Results from MPTP toxicity and APP + uptake assays indicate that the surface expression of DAT was reduced by BPA treatment. Immunofluorescence staining of neurons in the Substantia nigra (SN) area of the mouse brain also revealed that DAT remains in the perinuclear region, indicating lower surface expression of DAT in the SN, playing important roles in reward and movement. We used another in vivo model, C. elegans, expressing GFP-tagged DAT-1 fusion protein and found that exposure to 50 µM BPA induced a significant increase in the frequency of body bends. However, the frequency of body bends was significantly reduced at 100 µM BPA, indicating biphasic effects of BPA. In conclusion, our results suggest that BPA contributes to the alterations of mice and worm behavior by reducing DAT expression on the surface of neurons via blocking of DAT trafficking.https://doi.org/10.1038/s41598-025-98084-yBisphenol ABrainBehaviorDopamine transporterDAT trafficking |
| spellingShingle | Yu Shi Xiaoye Feng Chang Y. Chung Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking Scientific Reports Bisphenol A Brain Behavior Dopamine transporter DAT trafficking |
| title | Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking |
| title_full | Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking |
| title_fullStr | Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking |
| title_full_unstemmed | Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking |
| title_short | Chronic adulthood exposure to bisphenol A causes behavioral changes via suppressing dopamine transporter trafficking |
| title_sort | chronic adulthood exposure to bisphenol a causes behavioral changes via suppressing dopamine transporter trafficking |
| topic | Bisphenol A Brain Behavior Dopamine transporter DAT trafficking |
| url | https://doi.org/10.1038/s41598-025-98084-y |
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