Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Effects of chronic desipramine treatment on hippocampal transcriptome in mice differing in response to antidepressants

ABSTRACT: Analysis of chronic treatment with a tricyclic antidepressant (desipramine) at gene expression level in hippocampus of mice bred for high (HA) or low (LA) swim stress-induced analgesia (SSIA). Total RNA obtained from isolated hippocampi of HA and LA mice subjected to 21 intraperitoneal injections of desipramine hydrochloride (7.5 mg/kg/day) compared to total RNA obtained from isolated hippocampi of HA and LA mice subjected to 21 intraperitoneal injections of saline.

ORGANISM(S): Mus musculus

SUBMITTER: Pawel Lisowski

PROVIDER: E-GEOD-27532 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: The objective of this study was to evaluate the transcriptomic consequence of chronic exposure to deficient and excessive arginine supply in MIN6 pancreatic beta cells and reveal the molecular mechanisms underlying beta cell function and insulin secretion to arginine administration. Methods: After overnight adhesion, the medium was removed, and the cells were incubated in fresh DMEM medium containing low-, standard- or high-arginine concentration (LA, SA and HA) for 24 h. Following the treatment, RNA was extracted from cells for transcriptome sequencing. Results: Transcriptomics analysis allowed the detection of 23,620 and 22,939 transcripts in the LA and HA samples, among which 7,591 (3,736 up- and 3,855 down-regulated) and 197 (111 up- and 86 down-regulated) genes were expressed differently compared with the SA treatment. One hundred and forty one DEGs were overlapped between LA vs. SA and HA vs. SA comparisons, which were mainly involved in DNA replication, organic hydroxy compound metabolism and cellular response to oxidative stress. GO functional enrichment analysis demonstrated that terms related to proteasomal protein catabolic process, mRNA processing and ATP metabolic process were highly disturbed by LA administration, while DEGs induced by HA were mainly enriched to ammonium ion metabolic process, mRNA export and sterol biosynthetic process. Morever, KEGG pathway analysis revealed that DEGs between LA and SA treatments were mainly functionally classified as involved in protein processing in endoplasmic reticulum and oxidative phosphorylation, while DNA replication, steroid biosynthesis and cell cycle had more counts and reached significant difference levels according to the DEGs triggered by HA. Conclusions: These results suggested that the disturbed carbohydrate, lipid and amino acid metabolisms as well as the decreased cell proliferation, increased apoptosis and elevated oxidative stress contributed to the reduced insulin secretion in beta cells induced by LA or HA administrations.

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Effects of chronic desipramine treatment on hippocampal transcriptome in mice differing in response to antidepressants

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