Sleep-Aiding Effect of Casein-Derived Peptide TPTLN and Its Underlying Mechanism
Objective:To investigate the sleep-aiding effect of casein-derived peptide TPTLN and explore its possible mechanism of action.Methods:Thirty mice were divided equally into three groups,an experimental,a positive control and a blank control group,which were gavaged with TPTLN at a dose of 5 mg/kg mb,intraperitoneally injected with diazepam at a dose of 1 mg/kg mb,and gavaged with sterilized water at a dose of 5 mg/kg mb,respectively.The body mass of all the mice was recorded every day.After 7 days of continuous administration,a sodium pentobarbital-induced sleep test was carried out to evaluate sleep quality.Following 4 more days of administration,the mice were euthanized and dissected to collect blood and tissue samples for analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the levels of 5-hydroxytryptamine(5-HT),γ-aminobutyric acid(GABA),5-hydroxyindoleacetic acid(5-HIAA),glutamate(Glu),β-endorphin(β-EP),cortisol,norepinephrine(NE)in the serum and brain tissue,and the GABA/Glu ratio was evaluated.Real-time quantitative polymerase chain reaction(qPCR)was used to detect the effect of TPTLN on the mRNA relative expression levels of γ-aminobutyric acid A receptor α1(GABAA-α1)and 5-hydroxytryptamine receptor 1A(5-HT1A)in the hypothalamus.Results:Compared with the control group,TPTLN and sodium pentobarbital synergistically increased the sleep onset rate to 100%,significantly shortened the sleep latency by 31.7%(P<0.05),and extended the sleep duration 2.1 times(P<0.05);increased the GABA/Glu ratio in the serum and brain tissue by 68.8%and 19.3%,respectively and significantly improved the excitation/inhibition imbalance(P<0.001,P<0.000 1)as evidenced by a 49.4%increase in the serum GABA level(P<0.001),a 7.6%increase in the brain 5-HT level,and a 24.3%and 23.4%decrease in the brain levels of cortisol and NE(P<0.05);and significantly up-regulated the expression levels of the GABAA-α1 and 5-HT1A genes 1.5 and 1.3 times,respectively(P<0.01,P<0.05).Conclusion:Casein-derived peptide TPTLN exhibited a favorable sleep-aiding effect,and the underlying mechanism may be associated with the regulation of GABAA-α1 and 5-HT1A expression levels,as well as the modulation of neurotransmitter contents including GABA,Glu,5-HT,cortisol and NE in the brain.
casein-derived peptidesleep aidneurotransmittersmechanism of action
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