Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model
ObjectiveOur study was designed to investigate whether the indoleamine-2,3-dioxygenase (IDO)-mediated kynurenine/tryptophan (KYN/TRP) pathway participates in the development of emotional deficits from ethanol addiction/withdrawal mice.MethodsThe expression of proinflammatory factors, including tumor...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00011/full |
| _version_ | 1819078883419357184 |
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| author | Xi Jiang Xi Jiang Qian Lin Lexing Xu Ziwei Chen Qizhi Yan Lei Chen Xuefeng Yu |
| author_facet | Xi Jiang Xi Jiang Qian Lin Lexing Xu Ziwei Chen Qizhi Yan Lei Chen Xuefeng Yu |
| author_sort | Xi Jiang |
| collection | DOAJ |
| description | ObjectiveOur study was designed to investigate whether the indoleamine-2,3-dioxygenase (IDO)-mediated kynurenine/tryptophan (KYN/TRP) pathway participates in the development of emotional deficits from ethanol addiction/withdrawal mice.MethodsThe expression of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), was tested by enzyme-linked immunosorbent assay (ELISA). The IDO levels in the hippocampus, cerebral cortex, and amygdala were measured by polymerase chain reaction (PCR) and western blot, and the neurotransmitters were tested by high performance liquid chromatography (HPLC). Emotional deficits of mice were evaluated by behavioral tests.ResultsExpression levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were increased in mice after 4 weeks of alcohol exposure. As for indoleamine 2,3-dioxygenase (IDO) expression, only the subtype IDO1 was found to increase at both mRNA level and protein level in all the tested brain regions of ethanol addiction/withdrawal mice. In behavioral tests, mice exposed to alcohol showed gradually declined memory function accompanied by anxiety-like and depressive-like behaviors. Meanwhile, increased expression of KYN, decreased expression of 5-HT, and abnormal expression of 3-HK and KA were found in the hippocampus, cerebral cortex, and amygdala of ethanol addiction/withdrawal mice. Interestingly, the IDO1 inhibitor, 1-methyl-L-tryptophan (1-MT), reversed all above alterations induced by ethanol in mice.ConclusionOur results suggested that the TRP/KYN pathway, medicated by IDO1, in the hippocampus, cerebral cortex, and amygdala, plays an important role in the development of emotional deficits caused by ethanol addiction and withdrawal. |
| first_indexed | 2024-12-21T19:20:10Z |
| format | Article |
| id | doaj.art-cc644797a97249eeae66bb4d3cf1eacb |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-21T19:20:10Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-cc644797a97249eeae66bb4d3cf1eacb2022-12-21T18:52:58ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-02-011410.3389/fncel.2020.00011482429Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse ModelXi Jiang0Xi Jiang1Qian Lin2Lexing Xu3Ziwei Chen4Qizhi Yan5Lei Chen6Xuefeng Yu7Department of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, ChinaMingzhou Hospital, Zhejiang University, Hangzhou, ChinaDepartment of Pharmacology & Toxicology, University of Louisville, Louisville, KY, United StatesDepartment of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, ChinaDepartment of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, ChinaShaoxing People’s Hospital, Zhejiang University School of Medicine, Shaoxing, ChinaDepartment of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, ChinaDepartment of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, ChinaObjectiveOur study was designed to investigate whether the indoleamine-2,3-dioxygenase (IDO)-mediated kynurenine/tryptophan (KYN/TRP) pathway participates in the development of emotional deficits from ethanol addiction/withdrawal mice.MethodsThe expression of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), was tested by enzyme-linked immunosorbent assay (ELISA). The IDO levels in the hippocampus, cerebral cortex, and amygdala were measured by polymerase chain reaction (PCR) and western blot, and the neurotransmitters were tested by high performance liquid chromatography (HPLC). Emotional deficits of mice were evaluated by behavioral tests.ResultsExpression levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were increased in mice after 4 weeks of alcohol exposure. As for indoleamine 2,3-dioxygenase (IDO) expression, only the subtype IDO1 was found to increase at both mRNA level and protein level in all the tested brain regions of ethanol addiction/withdrawal mice. In behavioral tests, mice exposed to alcohol showed gradually declined memory function accompanied by anxiety-like and depressive-like behaviors. Meanwhile, increased expression of KYN, decreased expression of 5-HT, and abnormal expression of 3-HK and KA were found in the hippocampus, cerebral cortex, and amygdala of ethanol addiction/withdrawal mice. Interestingly, the IDO1 inhibitor, 1-methyl-L-tryptophan (1-MT), reversed all above alterations induced by ethanol in mice.ConclusionOur results suggested that the TRP/KYN pathway, medicated by IDO1, in the hippocampus, cerebral cortex, and amygdala, plays an important role in the development of emotional deficits caused by ethanol addiction and withdrawal.https://www.frontiersin.org/article/10.3389/fncel.2020.00011/fullethanol addictionindoleamine 23-dioxygenasedepressionanxietymemory |
| spellingShingle | Xi Jiang Xi Jiang Qian Lin Lexing Xu Ziwei Chen Qizhi Yan Lei Chen Xuefeng Yu Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model Frontiers in Cellular Neuroscience ethanol addiction indoleamine 2 3-dioxygenase depression anxiety memory |
| title | Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model |
| title_full | Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model |
| title_fullStr | Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model |
| title_full_unstemmed | Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model |
| title_short | Indoleamine-2,3-Dioxygenase Mediates Emotional Deficits by the Kynurenine/Tryptophan Pathway in the Ethanol Addiction/Withdrawal Mouse Model |
| title_sort | indoleamine 2 3 dioxygenase mediates emotional deficits by the kynurenine tryptophan pathway in the ethanol addiction withdrawal mouse model |
| topic | ethanol addiction indoleamine 2 3-dioxygenase depression anxiety memory |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00011/full |
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