Effects of brain peptides on 5-hydroxytryptamine system and intestinal flora in PCPA induced sleep disorder mice
This work studied the impact of brain peptide(BP)on sleep and intestinal microbiota in mice,and analyzed the relationship between intestinal microbiota and sleep through changes in neurotransmitter content and oxidative stress levels in mice.The insomnia model was established by peritoneal injection of p-chlorophenylalanine(PCPA),which was administered via continuous gavage for 7 days.The sedative and hypnotic effects of brain peptides on insomniac mice were analyzed by using a pentobarbital sodium sleep coordination test,tail suspension test(TST),light and dark box test(LDB),along with measurements of neurotransmitter levels and oxidative stress markers.Hematoxylin-eosin staining(H&E)and glycogen staining(AB-PAS)were used to observe histopathological changes in the hippocampus and colon of mice.The stool was collected and 16S rRNA gene was sequenced to analyze the changes of intestinal flora abundance in mice.Compared with the model group,the sleep latency of mice in the high-dose and low-dose brain polypeptide groups was significantly shortened,and the sleep time was significantly increased.MDA content decreased significantly,5-HT,GABA and MT content,the enzyme activity of GSH-Px and SOD increased significantly in high-dose brain polypeptide group(P＜0.05).The neuronal cells in CA1 region of hippocampus of mice were arranged neatly,the phenomenon of nuclear shrinkage and deep staining was improved,and the infiltration of inflammatory cells in colon tissue was reduced.16S rRNA results showed that compared with the model group,the abundance of Bacteroidetes was significantly increased in the high-dose BP group at the phylum level,and the abundance of Lactobacillus and Bifidobacterium at the genus level was significantly increased(P＜0.05).Pearson correlation analysis showed that the abundances of Bacteroides was positively correlated with the trends of GSH-Px,and the abundances of Lactobacillus was positively correlated with the trend of 5-HT,MT and SOD(P＜0.05).Brain polypeptide can effectively treat PCPA induced insomnia in mice by regulating intestinal flora and positively regulating serum neurotransmitter and brain tissue oxidative stress level,and the therapeutic effect is better with the increase of dose.
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