Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia
BackgroundParaquat (PQ) is a widely used herbicide that exerts neurotoxicity. The effects of PQ on neural stem cells (NSCs) through microglia mediated neuroinflammation remain limitedly studied. ObjectiveTo investigate the effects of PQ on the proliferation and neurogenesis of NSCs through neuroinfl...
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| Format: | Article |
| Language: | English |
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Editorial Committee of Journal of Environmental and Occupational Medicine
2022-09-01
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| Series: | 环境与职业医学 |
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| Online Access: | http://www.jeom.org/article/cn/10.11836/JEOM21605 |
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| author | Qian LI Hongxi XIAO Rui LI Liming TANG Xiuli CHANG Zhijun ZHOU |
| author_facet | Qian LI Hongxi XIAO Rui LI Liming TANG Xiuli CHANG Zhijun ZHOU |
| author_sort | Qian LI |
| collection | DOAJ |
| description | BackgroundParaquat (PQ) is a widely used herbicide that exerts neurotoxicity. The effects of PQ on neural stem cells (NSCs) through microglia mediated neuroinflammation remain limitedly studied. ObjectiveTo investigate the effects of PQ on the proliferation and neurogenesis of NSCs through neuroinflammation mediated by microglia.MethodsMicroglial cell lines (BV2 cells) and primary NSCs were used. BV2 cells were exposed to 0, 1, 3.3, 10, 33, and 100 μmol·L−1 of PQ for 6 h followed by viability assessment. The highest PQ concentration that had no effect on cell viability was selected as the final exposure concentration (33 μmol·L−1). To exclude the direct effect of PQ on NSCs, after the BV2 cells were cultured in complete medium containing 33 μmol·L−1 PQ for 6 h, the BV2 culture medium was replaced by NSCs complete medium without PQ for 24 h. The concentration of interleukin-1β (IL-1β) in supernatant was detected by enzyme-linked immune sorbent assay. Besides, in order to detect the effects of IL-1β on NSCs proliferation and neurogenesis, NSCs isolated from hippocampus of adult mice were cultured in the supernatant obtained above and divided into four groups: control supernatant + control antibody, control supernatant + IL-1β neutralizing antibody (10 ng·mL−1), PQ supernatant + control antibody, PQ supernatant + IL-1β neutralizing antibody (10 ng·mL−1). Proportion of Ki67-positive NSCs was detected by flow cytometry (FCS) and immunofluorescence after 24 h culture, and neurogenesis was detected by FCS and immunofluorescence after 3-7 d of culture. ResultsThe IL-1β concentration in the supernatant of BV2 cells was significantly increased after the 33 μmol·L−1 PQ exposure compared with the control group (t=3.020, P<0.05). After the NSCs were cultured with the supernatant of PQ-treated BV2 cells, the proportion of Ki67-positive NSCs (t=9.129, P<0.01) and the proportion of newborn neurons (t=4.638, P<0.01) were significantly decreased compared to the control group. After neutralizing IL-1β, the proportion of Ki67-positive NSCs (t=22.05, P<0.01) and the proportion of newborn neurons (t=11.09, P<0.01) were significantly higher than those in the un-neutralized group. The results of immunofluorescence detection also showed that after neutralizing IL-1β secreted by 33 μmol·L−1 PQ-treated BV2 cells, the number of Ki67-positive NSCs and the number of newborn neurons were significantly higher than those in the un-neutralized group. ConclusionThe secretion of IL-1β by microglia is increased after PQ treatment, resulting in a decrease in the proliferation and neurogenesis of NSCs. These results suggest that neuroinflammation is involved in NSCs damage caused by PQ. |
| first_indexed | 2024-04-12T13:27:37Z |
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| issn | 2095-9982 |
| language | English |
| last_indexed | 2024-04-12T13:27:37Z |
| publishDate | 2022-09-01 |
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| series | 环境与职业医学 |
| spelling | doaj.art-bfda8b5f5eae4471bec10a4627cd654a2022-12-22T03:31:16ZengEditorial Committee of Journal of Environmental and Occupational Medicine环境与职业医学2095-99822022-09-013991045105010.11836/JEOM2160521605Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microgliaQian LI0Hongxi XIAO1Rui LI2Liming TANG3Xiuli CHANG4Zhijun ZHOU5Department of Preventive Medicine, School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai 200032, ChinaPharmacology and Toxicology Department, Shanghai Institute for Drug and Food Control, Shanghai 201203, ChinaPharmacology and Toxicology Department, Shanghai Institute for Drug and Food Control, Shanghai 201203, ChinaSchool of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai 200032, ChinaSchool of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai 200032, ChinaBackgroundParaquat (PQ) is a widely used herbicide that exerts neurotoxicity. The effects of PQ on neural stem cells (NSCs) through microglia mediated neuroinflammation remain limitedly studied. ObjectiveTo investigate the effects of PQ on the proliferation and neurogenesis of NSCs through neuroinflammation mediated by microglia.MethodsMicroglial cell lines (BV2 cells) and primary NSCs were used. BV2 cells were exposed to 0, 1, 3.3, 10, 33, and 100 μmol·L−1 of PQ for 6 h followed by viability assessment. The highest PQ concentration that had no effect on cell viability was selected as the final exposure concentration (33 μmol·L−1). To exclude the direct effect of PQ on NSCs, after the BV2 cells were cultured in complete medium containing 33 μmol·L−1 PQ for 6 h, the BV2 culture medium was replaced by NSCs complete medium without PQ for 24 h. The concentration of interleukin-1β (IL-1β) in supernatant was detected by enzyme-linked immune sorbent assay. Besides, in order to detect the effects of IL-1β on NSCs proliferation and neurogenesis, NSCs isolated from hippocampus of adult mice were cultured in the supernatant obtained above and divided into four groups: control supernatant + control antibody, control supernatant + IL-1β neutralizing antibody (10 ng·mL−1), PQ supernatant + control antibody, PQ supernatant + IL-1β neutralizing antibody (10 ng·mL−1). Proportion of Ki67-positive NSCs was detected by flow cytometry (FCS) and immunofluorescence after 24 h culture, and neurogenesis was detected by FCS and immunofluorescence after 3-7 d of culture. ResultsThe IL-1β concentration in the supernatant of BV2 cells was significantly increased after the 33 μmol·L−1 PQ exposure compared with the control group (t=3.020, P<0.05). After the NSCs were cultured with the supernatant of PQ-treated BV2 cells, the proportion of Ki67-positive NSCs (t=9.129, P<0.01) and the proportion of newborn neurons (t=4.638, P<0.01) were significantly decreased compared to the control group. After neutralizing IL-1β, the proportion of Ki67-positive NSCs (t=22.05, P<0.01) and the proportion of newborn neurons (t=11.09, P<0.01) were significantly higher than those in the un-neutralized group. The results of immunofluorescence detection also showed that after neutralizing IL-1β secreted by 33 μmol·L−1 PQ-treated BV2 cells, the number of Ki67-positive NSCs and the number of newborn neurons were significantly higher than those in the un-neutralized group. ConclusionThe secretion of IL-1β by microglia is increased after PQ treatment, resulting in a decrease in the proliferation and neurogenesis of NSCs. These results suggest that neuroinflammation is involved in NSCs damage caused by PQ.http://www.jeom.org/article/cn/10.11836/JEOM21605paraquatmicrogliainterleukin-1βneural stem cellneurogenesis |
| spellingShingle | Qian LI Hongxi XIAO Rui LI Liming TANG Xiuli CHANG Zhijun ZHOU Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia 环境与职业医学 paraquat microglia interleukin-1β neural stem cell neurogenesis |
| title | Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia |
| title_full | Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia |
| title_fullStr | Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia |
| title_full_unstemmed | Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia |
| title_short | Effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of IL-1β by microglia |
| title_sort | effects of paraquat on proliferation and neurogenesis of neural stem cells by promoting secretion of il 1β by microglia |
| topic | paraquat microglia interleukin-1β neural stem cell neurogenesis |
| url | http://www.jeom.org/article/cn/10.11836/JEOM21605 |
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