Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells
Bisphenol-A (BPA) is a lipophilic, organic, synthetic compound that has been used as an additive in polycarbonate plastics manufacturing since 1957. Studies have shown that BPA interferes with the development and functions of the brain, but little is known about the effects of BPA on human glutamate...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Environment International |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412018326357 |
| _version_ | 1819078714597572608 |
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| author | Hongou Wang Lawrence Chang Jose S. Aguilar Sijun Dong Yiling Hong |
| author_facet | Hongou Wang Lawrence Chang Jose S. Aguilar Sijun Dong Yiling Hong |
| author_sort | Hongou Wang |
| collection | DOAJ |
| description | Bisphenol-A (BPA) is a lipophilic, organic, synthetic compound that has been used as an additive in polycarbonate plastics manufacturing since 1957. Studies have shown that BPA interferes with the development and functions of the brain, but little is known about the effects of BPA on human glutamatergic neurons (hGNs) at the molecular and cellular levels. We investigated the impact of chronic exposure to BPA to hGNs derived from human embryonic stem cells (hESCs). The results showed that chronic exposure of different concentrations of BPA (0, 0.1, 1.0 and 10 μM) to hGNs for 14 days reduced neurite outgrowth in a concentration-dependent manner. Using presynaptic protein synaptophysin and postsynaptic protein PSD-95 antibodies, immunofluorescence staining and western blotting results indicated that BPA exposure altered the morphology of dendritic spines and increased synaptophysin and PSD-95 expression. Furthermore, BPA exposure at concentrations higher than 1.0 μM resulted in the increase of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and deterioration of dendritic spines. In addition, our results suggested that these BPA mediated neurotoxicity effects were due to an increased production of reactive nitrogen species (RNS) and reactive oxygen species (ROS) via increased nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine expression and Ca2+ influx. These results imply that hESC-based neuronal differentiation is an excellent cellular model to examine BPA-induced neurotoxicity on human neurons at the cellular and molecular level. Keywords: Bisphenol-A, Human embryonic stem cell neuronal differentiation, Glutamatergic neurons, Synaptophysin, Postsynaptic density 95, α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors |
| first_indexed | 2024-12-21T19:17:29Z |
| format | Article |
| id | doaj.art-5a1a2aef708742d88598829cd63b1eca |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-12-21T19:17:29Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-5a1a2aef708742d88598829cd63b1eca2022-12-21T18:53:02ZengElsevierEnvironment International0160-41202019-06-01127324332Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cellsHongou Wang0Lawrence Chang1Jose S. Aguilar2Sijun Dong3Yiling Hong4College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, ChinaCollege of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USACenter for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Correspondence to: S. Dong, No. 1799, Jimei Road, Jimei District, Xiamen, Fujian 361021, China.College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Correspondence to: Y. Hong, 309 East Second Street, Pomona, CA 91766-1854, USA.Bisphenol-A (BPA) is a lipophilic, organic, synthetic compound that has been used as an additive in polycarbonate plastics manufacturing since 1957. Studies have shown that BPA interferes with the development and functions of the brain, but little is known about the effects of BPA on human glutamatergic neurons (hGNs) at the molecular and cellular levels. We investigated the impact of chronic exposure to BPA to hGNs derived from human embryonic stem cells (hESCs). The results showed that chronic exposure of different concentrations of BPA (0, 0.1, 1.0 and 10 μM) to hGNs for 14 days reduced neurite outgrowth in a concentration-dependent manner. Using presynaptic protein synaptophysin and postsynaptic protein PSD-95 antibodies, immunofluorescence staining and western blotting results indicated that BPA exposure altered the morphology of dendritic spines and increased synaptophysin and PSD-95 expression. Furthermore, BPA exposure at concentrations higher than 1.0 μM resulted in the increase of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and deterioration of dendritic spines. In addition, our results suggested that these BPA mediated neurotoxicity effects were due to an increased production of reactive nitrogen species (RNS) and reactive oxygen species (ROS) via increased nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine expression and Ca2+ influx. These results imply that hESC-based neuronal differentiation is an excellent cellular model to examine BPA-induced neurotoxicity on human neurons at the cellular and molecular level. Keywords: Bisphenol-A, Human embryonic stem cell neuronal differentiation, Glutamatergic neurons, Synaptophysin, Postsynaptic density 95, α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptorshttp://www.sciencedirect.com/science/article/pii/S0160412018326357 |
| spellingShingle | Hongou Wang Lawrence Chang Jose S. Aguilar Sijun Dong Yiling Hong Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells Environment International |
| title | Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| title_full | Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| title_fullStr | Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| title_full_unstemmed | Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| title_short | Bisphenol-A exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| title_sort | bisphenol a exposure induced neurotoxicity in glutamatergic neurons derived from human embryonic stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S0160412018326357 |
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