Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways
Anxiety is a multifaceted emotional response exhibited by animals when confronted with potential threats. Among most vertebrates, including mammals and fish, there is a pronounced sexual dimorphism in anxiety responses, with females typically demonstrating higher anxiety levels than males. Concurren...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Marine Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmars.2025.1541351/full |
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| author | Hong Tao Hong Tao Ying–Ying Zhang Ying–Ying Zhang Yan–Jun Shen Yan–Jun Shen Qi–Liang Chen Qi–Liang Chen Zhi–Hao Liu Zhi–Hao Liu |
| author_facet | Hong Tao Hong Tao Ying–Ying Zhang Ying–Ying Zhang Yan–Jun Shen Yan–Jun Shen Qi–Liang Chen Qi–Liang Chen Zhi–Hao Liu Zhi–Hao Liu |
| author_sort | Hong Tao |
| collection | DOAJ |
| description | Anxiety is a multifaceted emotional response exhibited by animals when confronted with potential threats. Among most vertebrates, including mammals and fish, there is a pronounced sexual dimorphism in anxiety responses, with females typically demonstrating higher anxiety levels than males. Concurrently, endogenous estrogen levels, specifically 17β-estradiol (E2), are significantly higher in females compared to males. This suggests a potential positive regulatory role of E2 on anxiety, contributing to sexually dimorphic anxiety in fish. To elucidate the role of E2 in mediating sexually dimorphic anxiety responses, male zebrafish (Danio rerio) were administered E2 (E2-M), while females were treated with letrozole (LET, an aromatase inhibitor that reduces E2 synthesis, LET-F) for 60 days, and plasma and brain levels of E2 were detected and anxiety response was evaluated by a novel tank diving test. Females (C-F) showed significantly higher anxiety responses, along with elevated E2 and cortisol levels in plasma and brain, and reduced brain serotonin (5-HT) and dopamine (DA) levels compared to males (C-M). Treatment with LET significantly decreased E2 levels in the plasma and brain of female zebrafish, which corresponded with reduced anxiety responses, lower plasma cortisol levels, and increased brain 5-HT and DA content. Additionally, the expression of genes associated with E2, cortisol, 5- HT, and DA pathways was relevantly altered. Conversely, E2 treatment in males (E2-M) increased E2 levels and anxiety responses, elevated plasma cortisol levels, and decreased brain 5-HT and DA content, with corresponding changes in gene expression. These findings strongly suggest that E2 positively regulates sexually dimorphic anxiety responses possibly by modulating plasma cortisol levels and the synthesis and action of 5-HT/DA in the brain. |
| format | Article |
| id | doaj-art-2fe4917db1c748d1a2f31cdf38e9e43e |
| institution | Kabale University |
| issn | 2296-7745 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Marine Science |
| spelling | doaj-art-2fe4917db1c748d1a2f31cdf38e9e43e2025-02-07T05:10:29ZengFrontiers Media S.A.Frontiers in Marine Science2296-77452025-02-011210.3389/fmars.2025.15413511541351Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathwaysHong Tao0Hong Tao1Ying–Ying Zhang2Ying–Ying Zhang3Yan–Jun Shen4Yan–Jun Shen5Qi–Liang Chen6Qi–Liang Chen7Zhi–Hao Liu8Zhi–Hao Liu9Chongqing Key Laboratory of Conservation and Utilization of Freshwater Fishes, Animal Biology Key Laboratory of Chongqing Education Commission of China, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaLaboratory of Water Ecological Health and Environmental Safety, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaChongqing Key Laboratory of Conservation and Utilization of Freshwater Fishes, Animal Biology Key Laboratory of Chongqing Education Commission of China, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaLaboratory of Water Ecological Health and Environmental Safety, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaChongqing Key Laboratory of Conservation and Utilization of Freshwater Fishes, Animal Biology Key Laboratory of Chongqing Education Commission of China, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaLaboratory of Water Ecological Health and Environmental Safety, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaChongqing Key Laboratory of Conservation and Utilization of Freshwater Fishes, Animal Biology Key Laboratory of Chongqing Education Commission of China, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaLaboratory of Water Ecological Health and Environmental Safety, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaChongqing Key Laboratory of Conservation and Utilization of Freshwater Fishes, Animal Biology Key Laboratory of Chongqing Education Commission of China, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaLaboratory of Water Ecological Health and Environmental Safety, College of Life Sciences, Chongqing Normal University, Chongqing, ChinaAnxiety is a multifaceted emotional response exhibited by animals when confronted with potential threats. Among most vertebrates, including mammals and fish, there is a pronounced sexual dimorphism in anxiety responses, with females typically demonstrating higher anxiety levels than males. Concurrently, endogenous estrogen levels, specifically 17β-estradiol (E2), are significantly higher in females compared to males. This suggests a potential positive regulatory role of E2 on anxiety, contributing to sexually dimorphic anxiety in fish. To elucidate the role of E2 in mediating sexually dimorphic anxiety responses, male zebrafish (Danio rerio) were administered E2 (E2-M), while females were treated with letrozole (LET, an aromatase inhibitor that reduces E2 synthesis, LET-F) for 60 days, and plasma and brain levels of E2 were detected and anxiety response was evaluated by a novel tank diving test. Females (C-F) showed significantly higher anxiety responses, along with elevated E2 and cortisol levels in plasma and brain, and reduced brain serotonin (5-HT) and dopamine (DA) levels compared to males (C-M). Treatment with LET significantly decreased E2 levels in the plasma and brain of female zebrafish, which corresponded with reduced anxiety responses, lower plasma cortisol levels, and increased brain 5-HT and DA content. Additionally, the expression of genes associated with E2, cortisol, 5- HT, and DA pathways was relevantly altered. Conversely, E2 treatment in males (E2-M) increased E2 levels and anxiety responses, elevated plasma cortisol levels, and decreased brain 5-HT and DA content, with corresponding changes in gene expression. These findings strongly suggest that E2 positively regulates sexually dimorphic anxiety responses possibly by modulating plasma cortisol levels and the synthesis and action of 5-HT/DA in the brain.https://www.frontiersin.org/articles/10.3389/fmars.2025.1541351/fullsexually dimorphic anxietyzebrafish17β-estradiolcortisolserotonindopamine |
| spellingShingle | Hong Tao Hong Tao Ying–Ying Zhang Ying–Ying Zhang Yan–Jun Shen Yan–Jun Shen Qi–Liang Chen Qi–Liang Chen Zhi–Hao Liu Zhi–Hao Liu Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways Frontiers in Marine Science sexually dimorphic anxiety zebrafish 17β-estradiol cortisol serotonin dopamine |
| title | Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways |
| title_full | Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways |
| title_fullStr | Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways |
| title_full_unstemmed | Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways |
| title_short | Endogenous 17β-estradiol regulates sexually dimorphic anxiety responses in zebrafish via the HPI axis and 5-HT/DA pathways |
| title_sort | endogenous 17β estradiol regulates sexually dimorphic anxiety responses in zebrafish via the hpi axis and 5 ht da pathways |
| topic | sexually dimorphic anxiety zebrafish 17β-estradiol cortisol serotonin dopamine |
| url | https://www.frontiersin.org/articles/10.3389/fmars.2025.1541351/full |
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