Chronic stress is a major inducer of anxiety and insomnia. Milk casein has been studied for its stress-relieving effects. We previously prepared a casein hydrolysate (CP) rich in the sleep-enhancing peptide YPVEPF, and this study aims to systemically investigate the different protective effects of CP and casein on dysfunction and anxiety/insomnia behavior and its underlying mechanisms in chronically stressed mice. Behavioral results showed that CP ameliorated stress-induced insomnia and anxiety more effectively than milk casein, and this difference in amelioration was highly correlated with an increase in GABA, 5-HT, GABA_A, 5-HT_1A receptors, and BDNF and a decrease in IL-6 and NMDA receptors in stressed mice. Furthermore, CP restored these dysfunctions in the brain and colon by activating the HPA response, modulating the ERK/CREB-BDNF-TrκB signaling pathway, and alleviating inflammation. The abundant YPVEPF (1.20 ± 0.04%) and Tyr-based/Trp-containing peptides of CP may be the key reasons for its different effects compared to casein. Thus, this work revealed the main active structures of CP and provided a novel dietary intervention strategy for the prevention and treatment of chronic-stress-induced dysfunction and anxiety/insomnia behaviors.

中文翻译：

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含 Tyr-Pro-Val-Glu-Pro-Phe 的酪蛋白水解物与酪蛋白对慢性应激性焦虑和失眠小鼠行为及周围神经和脑功能的保护作用比较


慢性压力是焦虑和失眠的主要诱因。人们已经研究了牛奶酪蛋白的缓解压力作用。我们之前制备了富含助眠肽YPVEPF的酪蛋白水解物（CP），本研究旨在系统研究CP和酪蛋白对慢性应激小鼠功能障碍和焦虑/失眠行为的不同保护作用及其潜在机制。行为结果表明，CP 比牛奶酪蛋白更有效地改善压力引起的失眠和焦虑，并且这种改善效果的差异与 GABA、5-HT、GABA _A 、5-HT _1A 受体和 BDNF，以及应激小鼠中 IL-6 和 NMDA 受体的减少。此外，CP 通过激活 HPA 反应、调节 ERK/CREB-BDNF-TrκB 信号通路和减轻炎症来恢复大脑和结肠的这些功能障碍。 CP中丰富的YPVEPF（1.20±0.04%）和含酪氨酸/色氨酸的肽可能是其与酪蛋白相比效果不同的关键原因。因此，这项工作揭示了CP的主要活性结构，并为预防和治疗慢性应激引起的功能障碍和焦虑/失眠行为提供了一种新颖的饮食干预策略。