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Series GSE83336 Query DataSets for GSE83336
Status Public on Jul 01, 2016
Title Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: implications for treatment-resistance
Organism Rattus norvegicus
Experiment type Expression profiling by high throughput sequencing
Summary Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less-known. We found that an epigenetic and energetic agent, acetyl-L-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line (FSL) rats. After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not respond (nrFSL). RNAseq for the ventral dentate-gyrus (vDG), a mood-regulatory region, identified metabolic factors as key markers predisposing to depression (insulin receptors Insr, glucose transporters Glut-4 and Glut-12, the regulator of appetite Cartpt) and to LAC responsiveness (leptin receptors Lepr, metabotropic glutamate receptors-2 mGlu2, neuropeptide-Y NPY, and mineralocorticoid receptors MR). Furthermore, we found that stress-induced treatment-resistance in nrFSL shows a new gene profile, including the metabolic regulator factors Elovl7 and Cyb5r2 and the synaptic regulator NPAS4. Finally, while improving central energy regulation and exerting rapid antidepressant-like effects, LAC corrected a systemic hyperinsulinemia and hyperglycemia.tance in rFSL and failed to do that in nrFSL. These findings establish CNS energy regulation as factor to be considered for the development of better therapeutics. Agents, like LAC, which regulate metabolic factors and reduce glutamate overflow, could rapidly ameliorate depression and could also be considered for treatment of insulin-resistance in depressed subjects. The approach here serves as a model for identifying markers and underlying mechanisms of predisposition to diseases and treatment responsiveness that may be useful in translation to human behavior and psychopathology.
Overall design Ventral dentate gyrus RNA from 3 biological replicates per group (vehicle-FRL, vehicle-FSL, LAC-treated not-responder FSL, LAC-treated responder FSL, all males) was used for library prep (TruSeq Stranded Total RNA with Ribo-Zero Human/Mouse/Rat) and sequenced on Illumina HiSeq2500 at the Genomic Core facility at The Rockefeller University. Each sample was provided with a unique adapter and all samples were put in the same pool and run in multiple lanes to control for lane effects with a sequencing depth of about 30M (100bp, single).
Contributor(s) Bigio B, Mathe' AA, Sousa VC, Zelli D, Svenningsson P, McEwen BS, Nasca C
Citation(s) 27354525
Submission date Jun 14, 2016
Last update date May 15, 2019
Contact name Carla Nasca
Organization name The Rockefeller University
Lab Neuroendocrinology
Street address 1230 York Avenue
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL18694 Illumina HiSeq 2500 (Rattus norvegicus)
Samples (12)
GSM2199650 FRL1
GSM2199651 FRL2
GSM2199652 FRL3
BioProject PRJNA325629
SRA SRP076539

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Supplementary file Size Download File type/resource
GSE83336_RAW.tar 850.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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