Mouse model of weak depression exhibiting suppressed cAMP signaling in amygdala, lower lipid catabolism in liver and correlated gut microbiota
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ABSTRACT:
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 to 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 the central nucleus of the amygdala (CeA) 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.
2013-07-20 | E-GEOD-49040 | biostudies-arrayexpress
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 – 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.
2013-07-20 | GSE49041 | GEO
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 – 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.
2013-07-20 | GSE49040 | GEO
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 – 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.
2013-07-20 | E-GEOD-49041 | biostudies-arrayexpress
Project description:E2 and GH are critical regulators of growth and intermediate metabolism in mammals. Hypothyroidism causes endocrine and metabolic disturbances in the liver with features that mimic deficiencies of E2 or GH signalling. In this work, we used the hypothyroid-orchiectomized (TXOX) adult rat model to evaluate the influence of E2 and GH on the liver in terms of global changes in gene expression. This study shows the changes in hepatic transcriptome that were provoked by E2 benzoate (50 ug/kg; sc; 5 days per week x 27 days), intermittent GH administration (0.3 mg/kg/day;sc injection divided into two daily injections x 7 days) or the combination of E2 plus GH in TXOX rats. E2 influenced the liver transcriptome, particularly genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, gender, and immune responses. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. Notably, the combination of E2 and GH caused deleterious effects on transcriptional immune response. These results highlight the role of E2 as a critical regulator of liver metabolism in mammals and provide insights into the functional interplay between E2 and GH in the liver. Groups=4; Biological replicates = 4 per group; Samples=16; Reference samples=TXOX group. Adult (3 months old) male Sprague-Dawley rats (n=4 per group) were used throughout these experiments. The generation of TXOX was performed by adding methimazole (MMI; 0.05%) to the drinking water for 5 weeks starting on postnatal day (PND) 59 until sacrifice on PND94. Two weeks after starting MMI administration, male rats were castrated (OX) to make TXOX rats. Four days after OX, we began treatment with E2 benzoate (TXOXE2) or vehicle (TXOX) to TXOX rats for 20 days followed for 7 days by either vehicle plus GH (TXOXGH) or by E2 plus GH (TXOXE2GH). Twenty-four hours (in the case of E2) or twelve hours (in the case of GH) after the last injection, the animals were killed by exsanguinations. Portions of the liver were snap frozen in liquid nitrogen and stored at -80C until processed for mRNA analysis.
2014-02-28 | E-GEOD-50014 | biostudies-arrayexpress
Project description:Background: As a worldwide threat to mental health, depression affects about 322 million people globally. Recently, the role of gut microbiota dysbiosis on the pathogenesis of depression has received widespread attention, but the underlying mechanism remains elusive.Results: Corticosterone (CORT)-treated mice showed depressive-like behaviors, a reduction in hippocampal neurogenesis, and an altered composition of gut microbiota (GM). Fecal microbial transplantation (FMT) from CORT-treated mice transferred depressive-like phenotypes and their dominant GM, especially bifidobacterium and lactobacillus, to the recipients. Fecal metabolic profiling showed that the relative abundances of fecal ceramides were significantly increased in CORT-treated and the recipient mice. Metagenomic sequencing exposed that bifidobacterium and lactobacillus might be responsible for gut ceramides production in CORT-treated mice. We then found that treatment with ceramides via oral gavage was sufficient to recapitulate the depressive-like phenotypes in wild -type mice. Finally, RNA-sequencing data exposed that most of the differentially expressed genes (DEGs) between ceramides-treated mice and the control group were enriched in oxidative phosphorylation (OXPHOS) pathway. Conclusion: We conclude that chronic exposure to CORT leads to an altered GM composition and consequent ceramides production, thus leading to subtle mitochondrial OXPHOS dysfunction in hippocampus, which may contribute to the development of depressive disorders.
2024-04-01 | GSE229237 | GEO
Project description:Chronic stressful situations contribute to the risk of developing depression. Using Genome-wide gene expression analysis, we analyzed the habenula transcriptome of rats exposed to chronic restraint stress for 14 days. We selected 379 differentially expressed genes (DEGs) affected by chronic stress. From 379 DEGs, neuroactive ligand-receptor interaction, cAMP signaling pathway, circadian entrainment and synaptic signaling on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, response to corticosteroid, positive regulation of lipid transport, anterograde trans-synaptic signaling, chemical synapse transmission on Gene Ontology (GO) pathway analysis was identified as significantly enriched pathways. We made a protein-protein interaction network of DEGs and analyzed subclusters, and neuroactive ligand-receptor interaction, circadian entrainment, and cholinergic synapse-related clusters were identified. To validate the findings, quantitative RT-PCR was done for significant genes. Identified DEGs and pathways could be important factors modulating habenular response to stress and lead to behavioral change. These data identify key molecular targets involved in chronic stress-induced depression within habenula and provides a valuable resource for future study.
2022-05-26 | GSE183386 | GEO
Project description:Administration of pivalate has been demonstrated to be suitable for induction of secondary car-nitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively charac-terize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of hepatic transcriptome and plasma metabolome of a total of 12, male 5-weeks-old pigs administered either pivalate (group PIV, n = 6) or vehicle (group CON, n = 6) for 28 days. Pigs of group PIV had approximately 40-60% lower concentrations of free carnitine and acetylcarnitine in plasma, liver and different skeletal muscles than pigs of group CON (p < 0.05). Transcript profiling of the liver revealed 140 differentially expressed genes (DEGs) between group PIV and group CON (fold change > 1.2 or < −1.2, p-value < 0.05). Biological process terms dealing with the innate immune response were found to be enriched with the DEGs (p < 0.05). Using a targeted metabolomics approach for the simultaneous quantification of 630 metabolites, 13 me-tabolites were identified to be lower and 5 metabolites to be higher in group PIV than in group CON (p < 0.05). Despite pivalate-induced CD caused only weak alterations of the hepatic tran-scriptome and the plasma metabolome, the changes observed indicate that secondary CD modu-lates the innate immune response of pigs.
2021-06-18 | GSE178384 | GEO
Project description:In humans there are sex-specific differences in the prevalence and symptomology of psychiatric disorders. However, preclinical animal models have primarily used males. As such, the molecular mechanisms underlying sex-specific differences in mental illness are not well established. In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala. We found a considerable number of differentially expressed genes (DEGs) between males and females across all brain regions. However, 84.9% of all DEGs were found in the NAcS (> 5000 genes; p < 0.01, FDR < 0.01). Relating these DEGs to genome wide association studies (GWAS) revealed an enrichment for loci associated with major depressive disorder (Psychiatric Genomics Consortium 2019). We compared the DEGs in the NAcS to an analgous human dataset (Labonte, 2017), and found 587 common DEGs which were enriched for genes associated with both anxiety (neuro genetics study, 2016) and broad depression (UK biobank, 2018). Our data provide comprehensive evidence of sex molecular profiles in the NAcS. Importantly these differences associate with anxiety and depression, suggesting an intrinsic molecular basis for sex-based differences in disease prevalence and presentation.
2020-12-02 | GSE162419 | GEO
Project description:Background. Food can affect the microbial balance in the human intestine, and the ingestion of probiotics may play a role in the current obesity pandemic. The objective of our study was to determine if increased Lactobacillus spp. in the intestinal microflora of mice can promote growth and if changes in the intestinal microflora are associated with modifications in metabolism. Methodology. Female BALBc mice were divided between one control and two experimental groups and inoculated either once or twice with 4×1010 Lactobacillus per animal in PBS or with PBS alone. Fecal samples were collected and tested using qPCR to detect and quantify Lactobacillus spp., Bacteroidetes and Firmicutes. Gene expression by microarray and RT-PCR was studied in liver and adipose tissue. Finally, metabolic parameters in the plasma were tested. Principal Findings. In three independent experiments, we observed an increase in both weight gain and liver weight in mice inoculated with 4×1010 Lactobacillus. Inoculation with Lactobacillus sp. (ostrich) increased the Lactobacillus spp. and Firmicutes DNA copy number in feces. The transcriptional profile of liver tissue from mice inoculated with Lactobacillus sp. (ostrich) was enriched for Gene Ontology terms related to the immune response and metabolic modifications. The mRNA levels of fatty acyl synthase (Fas), sterol regulatory element binding factor 1 (Srebp1c), tumor necrosis factor alpha (Tnf), cytochrome P450 2E1 (Cyp2e1) and 3-phosphoinositide-dependent protein kinase-1 (Pdpk1) were significantly elevated in liver tissue in experimental group animals. In gonadal adipose tissue, the expression of leptin, peroxisome proliferator-activated receptor gamma (Pparg and Srebp1c was significantly higher in experimental group animals, whereas the expression of adiponectin was significantly lower. Conclusions. Alterations in the intestinal microbiota resulted in increased weight gain. Furthermore, increased Lactobacillus spp. in the intestinal microflora of mice inoculated with Lactobacillus sp. (ostrich) resulted in accelerated weight gain, liver enlargement and metabolic changes in the plasma, liver and adipose tissue.
2010-09-21 | GSE24219 | GEO