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Series GSE81672 Query DataSets for GSE81672
Status Public on Jul 27, 2016
Title Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical.
Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala.
Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied.
Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine.
 
Overall design mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.
 
Contributor(s) Bagot RC, Cates HM, Nestler EJ
Citation(s) 27569543
Submission date May 20, 2016
Last update date Jul 10, 2019
Contact name Immanuel Purushothaman
E-mail(s) immanuel.purushothaman@mssm.edu
Organization name Icahn School of Medicine at Mount Sinai
Department Neuroscience
Street address 1425 Madison Avenue
City New York
State/province New York
ZIP/Postal code 10029
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (99)
GSM2166101 Sample 1: PFC_control_saline
GSM2166102 Sample 2: PFC_resilient_saline
GSM2166103 Sample 3: PFC_susceptible_saline
Relations
BioProject PRJNA322294
SRA SRP075473

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE81672_HTSeq_counts_matrix.xls.gz 13.7 Mb (ftp)(http) XLS
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Raw data are available in SRA
Processed data are available on Series record
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