T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice
The T-2 toxin is a frequent contaminant in the global environment and agricultural production. Existing evidence suggests that the ingested T-2 toxin can enter the brain and exhibit neurotoxicity. However, it is still unknown whether T-2 toxin causes the depression-like behaviors. In this study, the...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324014684 |
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| author | Zhigang Chen Shaoyi Duan Jialu Li Jianming Su Hongyu Lei |
| author_facet | Zhigang Chen Shaoyi Duan Jialu Li Jianming Su Hongyu Lei |
| author_sort | Zhigang Chen |
| collection | DOAJ |
| description | The T-2 toxin is a frequent contaminant in the global environment and agricultural production. Existing evidence suggests that the ingested T-2 toxin can enter the brain and exhibit neurotoxicity. However, it is still unknown whether T-2 toxin causes the depression-like behaviors. In this study, the mice were orally administrated with 1.5 mg/kg T-2 toxin daily for 14 d, and the depression-like behaviors were assessed by the tail suspension test (TST) and sucrose preference test (SPT). Here, the results showed that T-2 toxin exposure induced depression-like behaviors, manifested as behavioral despair and anhedonia, without anxiety-like behaviors. In addition, the reduced dopamine (DA) level and elevated dopamine transporter (DAT) level were found in reward center nucleus accumbens (NAc) receiving DAergic projection from ventral tegmental area (VTA) in brain after T-2 toxin administration, while there was no significant alteration in DA synthesis-related tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in VTA and DA storage-related vesicle monoamine transporter 2 (VMAT2) in NAc. The local administration of DAT inhibitor AHN 1–055 hydrochloride into NAc alleviated T-2 toxin caused the depression-like behaviors. Importantly, the chemogenetic activation of the VTADA-NAc circuit increased the DA content in NAc and reversed the T-2 toxin-produced behavioral despair and anhedonia. Thus, our study for the first time illustrates DA dysregulation by upregulated DAT in NAc mediates T-2 toxin-triggered depression-like symptoms in mice. Meanwhile, this study establishes a novel causal relation between the neurotoxicant T-2 toxin exposure and the etiology of depression-like behaviors, and provides reference for the prevention and treatment for mycotoxin-induced depression-like symptoms. |
| format | Article |
| id | doaj-art-bbfc6901a8b744128093372c33c36539 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-bbfc6901a8b744128093372c33c365392025-01-23T05:25:26ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117392T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male miceZhigang Chen0Shaoyi Duan1Jialu Li2Jianming Su3Hongyu Lei4College of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, ChinaCorresponding author.; College of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, ChinaThe T-2 toxin is a frequent contaminant in the global environment and agricultural production. Existing evidence suggests that the ingested T-2 toxin can enter the brain and exhibit neurotoxicity. However, it is still unknown whether T-2 toxin causes the depression-like behaviors. In this study, the mice were orally administrated with 1.5 mg/kg T-2 toxin daily for 14 d, and the depression-like behaviors were assessed by the tail suspension test (TST) and sucrose preference test (SPT). Here, the results showed that T-2 toxin exposure induced depression-like behaviors, manifested as behavioral despair and anhedonia, without anxiety-like behaviors. In addition, the reduced dopamine (DA) level and elevated dopamine transporter (DAT) level were found in reward center nucleus accumbens (NAc) receiving DAergic projection from ventral tegmental area (VTA) in brain after T-2 toxin administration, while there was no significant alteration in DA synthesis-related tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) in VTA and DA storage-related vesicle monoamine transporter 2 (VMAT2) in NAc. The local administration of DAT inhibitor AHN 1–055 hydrochloride into NAc alleviated T-2 toxin caused the depression-like behaviors. Importantly, the chemogenetic activation of the VTADA-NAc circuit increased the DA content in NAc and reversed the T-2 toxin-produced behavioral despair and anhedonia. Thus, our study for the first time illustrates DA dysregulation by upregulated DAT in NAc mediates T-2 toxin-triggered depression-like symptoms in mice. Meanwhile, this study establishes a novel causal relation between the neurotoxicant T-2 toxin exposure and the etiology of depression-like behaviors, and provides reference for the prevention and treatment for mycotoxin-induced depression-like symptoms.http://www.sciencedirect.com/science/article/pii/S0147651324014684T-2 toxinDepression-like behaviorsDopamine transporterVentral tegmental areaNucleus accumbensChemogenetic activation |
| spellingShingle | Zhigang Chen Shaoyi Duan Jialu Li Jianming Su Hongyu Lei T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice Ecotoxicology and Environmental Safety T-2 toxin Depression-like behaviors Dopamine transporter Ventral tegmental area Nucleus accumbens Chemogenetic activation |
| title | T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| title_full | T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| title_fullStr | T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| title_full_unstemmed | T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| title_short | T-2 toxin triggers depression-like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| title_sort | t 2 toxin triggers depression like behaviors via upregulation of dopamine transporter in nucleus accumbens of male mice |
| topic | T-2 toxin Depression-like behaviors Dopamine transporter Ventral tegmental area Nucleus accumbens Chemogenetic activation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324014684 |
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