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Mouse model of weak depression exhibiting suppressed cAMP signaling in amygdala, lower lipid catabolism in liver and correlated gut microbiota

ABSTRACT: To establish a mouse model of weak depression, we raised six-week-old C57BL/6N mice in single (SH) or group housing (GH) conditions for two weeks. The SH group showed less social interaction with stranger mice, learning disability in behavioral tests, and lower plasma corticosterone level. The cecal microbiota of the SH group showed significant segregation from the GH group in principal coordinate analysis. Transcriptome analysis of the amygdala, and liver detected multiple differentially expressed genes (DEGs). In the amygdala of SH mice, suppression of the cyclic adenine monophosphate (cAMP) signal was predicted and confirmed by the reduced immunoreactivity of phosphorylated cAMP-responsive element binding protein. In the liver of SH mice, down-regulation of beta-oxidation was predicted. Interestingly, the expression levels of over 100 DEGs showed significant correlation with the occupancy of two bacterial genera, Lactobacillus (Lactobacillaceae) and Anaerostipes (Lachnospiraceae). These bacteria-correlated DEGs included JunB, the downstream component of cAMP signaling in the amygdala, and carnitine palmitoyltransferase 1A, a key enzyme of beta-oxidation in the liver. This trans-omical analysis also suggested that NAD synthesis in the liver may be linked to the occupancy of Lactobacillus through the regulation of nicotinamide phosphoribosyltransferase and kynureninase genes. Our results suggested that SH condition along with the presence of correlated bacteria species causes weak depression phenotype in young mice and provide suitable model to study food ingredient that is able to cure weak depression.

ORGANISM(S): Mus musculus

PROVIDER: GSE198597 | GEO | 2022/07/19

REPOSITORIES: GEO

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Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 ‚Äì 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in brain nucleus accumbens shell (Acb-sh) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.

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Mouse model of weak depression exhibiting suppressed cAMP signaling in amygdala, lower lipid catabolism in liver and correlated gut microbiota

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