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Sea Cucumber Phospholipids Improve Chronic Stress-induced Depression-like Behavior in Zebrafish by Regulating the TRP-KYN Pathway
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    Abstract:

    To investigate the effects of sea cucumber phospholipids on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in zebrafish and associated mechanisms, Zebrafish were randomly divided into a control group, a stress group, a stress+low-dose (50 mg/kg) sea cucumber phospholipids intervention group, and a stress+high-dose (100 mg/kg) sea cucumber phospholipid intervention group. After the stress period, the novel tank and light-dark box behavioral tests were performed, the contents of interleukin (IL)-10, IL-6, indoleamine-2,3-dioxygenase (IDO), Tryptophan (TRP) and Kynurenine (KYN) were determined by enzyme linked immunosorbent assay (ELISA), whilst the level of 5-hydroxytryptamine (5-HT) was detected by high performance liquid chromatography (HPLC). Compared with the stress group, the depression degree of zebrafish in the low (50 mg/kg) and high dose (100 mg/kg) sea cucumber phospholipid groups was effectively reduced as shown in the new tank and the light-dark box behavior tests. Their contents of IL-10 in the brain increased by 12.05% and 15.26% (P<0.05 and P<0.01), contents of IL-6 decreased by 12.23% and 14.87% (P<0.01 and P<0.000 1), activities of IDO decreased by 14.12% and 22.20% (P<0.01 and P<0.000 1), and contents of TRP increased by 4.07% and 4.33% (P<0.05), contents of KYN decreased by 6.83% and 8.67% (P<0.05), ratios of KYN/TRP decreased by 9.43% and 11.32% (P<0.05), and contents of 5-HT increased by 28.57% (P<0.05) respectively. Therefore, depression can be ameliorated by sea cucumber phospholipids. The mechanisms include the amelioration of inflammation and reduction of 5-HT synthesis caused by the activation of TRP-KYN pathway by IDO. This study provides new ideas for the development of antidepressant products by using sea cucumber phospholipids.

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History
  • Received:October 26,2024
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  • Online: March 12,2026
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