Research Laboratories for Health Science & Food Technologies, Kirin Company Ltd, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan.
Division of Pharmacology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Nutrients. 2019 Feb 6;11(2):348. doi: 10.3390/nu11020348.
Tryptophan-tyrosine (WY)-related peptides including the β-lactopeptide of the glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improve spatial memory. However, whether and how the WY dipeptide as the core sequence in WY-related peptides improves memory functions has not been investigated. This study assessed the pharmacological effects of the WY dipeptide on memory impairment to elucidate the mechanisms. Here, we showed that oral administration of dipeptides of WY, tryptophan-methionine (WM), tryptophan-valine, tryptophan-leucine, and tryptophan-phenylalanine improved spontaneous alternation of the Y-maze test in scopolamine-induced amnesic mice. In contrast, tyrosine-tryptophan, methionine-tryptophan, tryptophan, tyrosine, and methionine had no effect. These results indicated that the conformation of dipeptides with N-terminal tryptophan is required for their memory improving effects. WY dipeptide inhibited the monoamine oxidase B activity in vitro and increased dopamine levels in the hippocampus and frontal cortex, whereas tryptophan did not cause these effects. In addition, the treatment with SCH-23390, a dopamine D1-like receptor antagonist, and the knockdown of the hippocampal dopamine D1 receptor partially attenuated the memory improvement induced by the WY dipeptide. Importantly, WY dipeptide improved the spontaneous alternations of the Y-maze test in aged mice. These results suggest that the WY dipeptide restores memory impairments by augmenting dopaminergic activity. The development of supplements rich in these peptides might help to prevent age-related cognitive decline.
色氨酰-酪氨酸（WY）相关肽，包括甘氨酰-苏氨酰-色氨酰-酪氨酸肽的β-内啡肽，β- lactolin，可改善空间记忆。然而，WY 二肽作为 WY 相关肽中的核心序列是否以及如何改善记忆功能尚未得到研究。本研究评估了 WY 二肽对记忆障碍的药理作用，以阐明其机制。在这里，我们表明，WY 二肽（色氨酰-蛋氨酸（WM）、色氨酰-缬氨酸、色氨酰-亮氨酸和色氨酰-苯丙氨酸）的口服给药可改善东莨菪碱诱导的健忘症小鼠的 Y 迷宫测试中的自发交替。相比之下，酪氨酸-色氨酸、蛋氨酸-色氨酸、色氨酸、酪氨酸和蛋氨酸没有效果。这些结果表明，具有 N 端色氨酸的二肽的构象是其改善记忆作用所必需的。WY 二肽在体外抑制单胺氧化酶 B 活性并增加海马和前额叶皮质中的多巴胺水平，而色氨酸则没有引起这些作用。此外，用多巴胺 D1 样受体拮抗剂 SCH-23390 处理和海马多巴胺 D1 受体的敲低部分减弱了 WY 二肽引起的记忆改善。重要的是，WY 二肽改善了老年小鼠 Y 迷宫测试中的自发交替。这些结果表明，WY 二肽通过增强多巴胺能活性来恢复记忆障碍。富含这些肽的补充剂的开发可能有助于预防与年龄相关的认知能力下降。
