γ-[Glu]_((1≤n≤4))-Trp改善斑马鱼焦虑样行为及五羟色胺合成的作用机制

Mechanism ofγ-[Glu]_((1≤n≤4))-Trp to Improve Anxious-like Behavior and Serotonin Synthesis in Zebrafish Model

该研究探讨了γ-[Glu]_((1≤n≤4))-Trp(EnW)及其四种肽单体(γ-Glu-Trp、γ-[Glu]_(2)-Trp、γ-[Glu]_(3)-Trp和γ-[Glu]_(4)-Trp)改善斑马鱼焦虑样行为和五羟色胺(Serotonin,5-HT)合成的作用机制。EnW及其肽单体均采用水溶给药的方式处理斑马鱼(低剂量56μg/mL、高剂量500μg/mL),各供试品处理2周后开始行为学和生化指标测试。与正常对照组相比,行为学研究结果表明EnW及其肽单体均能够增加斑马鱼黑白偏好实验中明区停留时间百分比、新鱼缸实验中上下穿梭次数和鱼缸上半部分停留时间百分比,其中γ-Glu-Trp组斑马明区停留时间百分比(41.66%)、上下穿梭次数(25.83次)和鱼缸上半部分的停留时间百分比(38.95%)增加最显著(p<0.05);此外,生化指标测定结果表明EnW及其肽单体增加了斑马鱼大脑组织色氨酸(Trp)浓度、色氨酸羟化酶活性和5-HT水平。综上所述,EnW及其肽单体作为Trp的直接来源改善斑马鱼焦虑样行为的可能作用机制是通过增加大脑组织Trp浓度,上调Trp-5-HT代谢途径进而增加神经递质5-HT的合成而发挥作用,从而证明膳食补充EnW及其肽单体具有预防和改善焦虑的作用。

The mechanism ofγ-[Glu]_((1≤n≤4))-Trp and its peptide monomers(γ-Glu-Trp,γ-[Glu]_(2)-Trp,γ-[Glu]_(3)-Trp,andγ-[Glu]_(4)-Trp)on anxiety-like behavior and serotonin synthesis was investigated using a zebrafish model.The anxiety-like behaviors(increased time in the light area in light-dark test,number of up-and-down shuttles in novel tank test)were reduced two weeks after administration of 56μg/mLγ-[Glu]_((1≤n≤4))-Trp and 500μg/mL of each monomer.γ-Glu-Trp was most effective(41.66%of time in light,25.83%up-and-down shuttles).γ-[Glu]_((1≤n≤4))-Trp and its peptide monomer induced up-regulation of tryptophan-serotonin(Trp-5-HT)metabolism by increasing Trp concentration and tryptophan hydroxylase activity in zebrafish.The in vivo findings demonstrate thatγ-[Glu]_((1≤n≤4))-Trp and its peptide monomer have significant anti-anxiety effects as evidenced by reduced anxiety-like behavior,increased 5-HT level,and induced up-regulation of Trp-5-HT metabolism pathway in zebrafish treated withγ-[Glu]_((1≤n≤4))-Trp and its peptide monomer compared to that in the control group.These results suggest that dietaryγ-[Glu]_((1≤n≤4))-Trp and its peptide monomer may induce beneficial effects for anxious behavior.