Proteomic analysis of the intestine reveals SNARE-mediated immunoregulatory and amino acid absorption perturbations in a rat model of depression
LIFE SCIENCES
Authors: Gong, Xue; Huang, Cheng; Yang, Xun; Mao, Qiang; Zeng, Li; Zheng, Peng; Pu, Juncai; Chen, Jianjun; Wang, Haiyang; Xu, Bing; Zhou, Chanjuan; Xie, Peng
Abstract
Aims: To clarify the role of the gut-brain axis in depression. Main methods: We used the iTRAQ technique to identify differential proteins in the intestine of the rat model of chronic unpredictable mild stress (CUMS)-induced depression. Significant differential proteins were subjected to Gene Ontology (GO) functional annotations and KEGG pathway enrichment analysis. Key proteins were validated at the mRNA and protein levels. The levels of cytokines in the intestine, serum and hypothalamus were examined by ELISA. HPLC-UV was used to detect the levels of amino acids. Key findings: In the rat intestine, 349 differential proteins (209 downregulated, 140 upregulated) were identified. GO analysis indicated that "protein complex assembly" was the first-ranked biological process. SNARE complex components, including SNAP23, VAMP3 and VAMP8, were increased at the mRNA levels, while only VAMP3 and VAMP8 were also upregulated at the protein level. TNF alpha, IL6 and IL1 beta were upregulated in the GUMS rat intestine, while TNF alpha was decreased in the serum and hypothalamus. IL1 beta was decreased in the serum. "Protein digestion and absorption" was the most significantly enriched KEGG pathway, involving 5 differential proteins: SLC9A3, ANPEP, LAT1, ASCT2 and B(0)AT1. Glutamine, glycine and aspartic acid were perturbed in the GUMS rat intestine. Significance: Our findings suggest that GUMS enhances the adaptive immune response in the intestine through ER-phagosome pathway mediated by SNARE complex and disturb absorption of amino acids. It advances our understanding of the role of gut-brain axis in depression and provides a potential therapeutic target for the disease.
Role of genetic variants at the neutral endopeptidase (MME) and aminopeptidase N (ANPEP) genes for enkephalin degradation in depression and anxiety.
MOLECULAR PSYCHIATRY
Authors: Comings, DE; Dietz, G; Gade-Andavolu, R; Blake, H; Muhleman, D; Huss, M; Saucier, G; MacMurray, JP
Abstract