Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis
Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems re...
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Elsevier
2025-08-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412025003824 |
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| author | Ya Wang Yuning Chen Houlin Chen James N Samsom Minfei Shu Xuehui Gao Qiyu Li Kangmin Chen Le Wang Fang Liu |
| author_facet | Ya Wang Yuning Chen Houlin Chen James N Samsom Minfei Shu Xuehui Gao Qiyu Li Kangmin Chen Le Wang Fang Liu |
| author_sort | Ya Wang |
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| description | Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems related to mood disorders. PFOA exposure (5 mg/kg) for 10 consecutive days caused depression-like behaviors in male mice. We measured increased corticosterone in serum and in the hippocampus of PFOA-exposed mice, which were linked to enhanced CRF expression measured in the PVN. Elevated corticosterone was associated with reductions in glucocorticoid receptor (GR) protein expression within the hippocampus. CRFR1 antagonist injected into the PVN and intracerebroventricular (i.c.v.) GR antagonist both reduced depression-like behaviors, respectively. In addition, NMDA-dependent Schaeffer collateral-CA3 synaptic transmission in PFOA-exposed mice was disrupted. Synaptic deficits could be corrected by either CRFR1 or GR antagonists. In summary, we found exposure of male mice to PFOA enhances CRF expression, which then activates the HPA axis to disrupt GR expression in the hippocampus, leading to depression-like behaviors. This data is relevant for understanding the potential harmful health effects of PFOA. |
| format | Article |
| id | doaj-art-9bb07db21877467e99caa5f424b4fdeb |
| institution | Kabale University |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj-art-9bb07db21877467e99caa5f424b4fdeb2025-08-20T03:24:16ZengElsevierEnvironment International0160-41202025-08-0120210963110.1016/j.envint.2025.109631Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axisYa Wang0Yuning Chen1Houlin Chen2James N Samsom3Minfei Shu4Xuehui Gao5Qiyu Li6Kangmin Chen7Le Wang8Fang Liu9Institute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, CanadaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR ChinaInstitute of Mental Health and Drug Discovery, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Psychiatry, Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada; Institute of Medical Science, University of Toronto, Canada; Departments of Pharmacology and Toxicology, University of Toronto, Canada; Department of Psychiatry, University of Toronto, Canada; Department of Physiology, University of Toronto, Canada; Corresponding author at: Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada.Perfluorooctanoic acid (PFOA), an environmental endocrine disruptor, has been found to increase the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN). In this study, adult male mice were given PFOA by oral gavage (p.o.) to evaluate whether it disrupts systems related to mood disorders. PFOA exposure (5 mg/kg) for 10 consecutive days caused depression-like behaviors in male mice. We measured increased corticosterone in serum and in the hippocampus of PFOA-exposed mice, which were linked to enhanced CRF expression measured in the PVN. Elevated corticosterone was associated with reductions in glucocorticoid receptor (GR) protein expression within the hippocampus. CRFR1 antagonist injected into the PVN and intracerebroventricular (i.c.v.) GR antagonist both reduced depression-like behaviors, respectively. In addition, NMDA-dependent Schaeffer collateral-CA3 synaptic transmission in PFOA-exposed mice was disrupted. Synaptic deficits could be corrected by either CRFR1 or GR antagonists. In summary, we found exposure of male mice to PFOA enhances CRF expression, which then activates the HPA axis to disrupt GR expression in the hippocampus, leading to depression-like behaviors. This data is relevant for understanding the potential harmful health effects of PFOA.http://www.sciencedirect.com/science/article/pii/S0160412025003824Perfluorooctanoic acid (PFOA)Depression-like behaviorscorticotropin-releasing factor (CRF)CorticosteroneGlucocorticoid Receptors (GRs) |
| spellingShingle | Ya Wang Yuning Chen Houlin Chen James N Samsom Minfei Shu Xuehui Gao Qiyu Li Kangmin Chen Le Wang Fang Liu Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis Environment International Perfluorooctanoic acid (PFOA) Depression-like behaviors corticotropin-releasing factor (CRF) Corticosterone Glucocorticoid Receptors (GRs) |
| title | Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis |
| title_full | Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis |
| title_fullStr | Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis |
| title_full_unstemmed | Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis |
| title_short | Exposure to “Forever Chemical” perfluorooctanoic acid induces depression-like behaviors in mice by activating the HPA axis |
| title_sort | exposure to forever chemical perfluorooctanoic acid induces depression like behaviors in mice by activating the hpa axis |
| topic | Perfluorooctanoic acid (PFOA) Depression-like behaviors corticotropin-releasing factor (CRF) Corticosterone Glucocorticoid Receptors (GRs) |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025003824 |
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