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Series GSE271600 Query DataSets for GSE271600
Status Public on Jul 05, 2024
Title Npbwr1 signaling mediates fast antidepressant action
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Chronic stress is a major risk factor for depression, a leading cause of disability and suicide. Because current antidepressants work slowly, have common side effects, and are only effective in a minority of patients, there is an unmet need to identify the underlying molecular mechanisms. Here, we identify the receptor for neuropeptides B and W, Npbwr1, as a key regulator of depressive-like symptoms. Npbwr1 is increased in the nucleus accumbens of chronically stressed mice and postmortem in patients diagnosed with depression. Using viral-mediated gene transfer, we demonstrate a causal link between Npbwr1, dendritic spine morphology, the biomarker Bdnf, and depressive-like behaviors. Importantly, microinjection of the synthetic antagonist of Npbwr1, CYM50769, rapidly ameliorates depressive-like behavioral symptoms and alters Bdnf levels. CYM50769 is selective, well tolerated, and shows effects up to 7 days after administration of a single dose. In summary, these findings advance our understanding of mood and chronic stress and warrant further investigation of CYM50769 as a potential fast-acting antidepressant.
 
Overall design Total mRNA sequenced 1) for 8 brain NAc (Nucleus accumbens) samples of 8 weeks old mice after stereotaxic surgery to infect NAc by empty Adeno-associated virus constructs (GFP control) and AAVs to overexpress (OE) Npbwr1. And 2) for 64 NAc samples at four time points in a 12L:12D light cycle and from two genotypes (C75BL/6J wild type and T75A-DARPP-32 mutant), 2 hours after injection with 7.5 mg/kg caffeine or saline at an injection volume of 10ml/kg body.
 
Contributor(s) Stein G, Aly JS, Lange L, Manzolillo A, Riege K, Brancato A, Hübner CA, Turecki G, Hoffmann S, Engmann O
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Submission date Jul 05, 2024
Last update date Jul 05, 2024
Contact name Konstantin Riege
E-mail(s) konstantin.riege@leibniz-fli.de
Organization name Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
Street address Beutenbergstraße 11
City Jena
ZIP/Postal code 07745
Country Germany
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (72)
GSM8380323 NAc_ctrl, rep1
GSM8380324 NAc_ctrl, rep2
GSM8380325 NAc_ctrl, rep3
Relations
BioProject PRJNA1132273

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
GSE271600_NAc-Npbwr1-counts.tsv.gz 581.1 Kb (ftp)(http) TSV
GSE271600_NAc-Npbwr1-tpm.tsv.gz 2.0 Mb (ftp)(http) TSV
GSE271600_NAc-Npbwr1-vsc.tsv.gz 1.7 Mb (ftp)(http) TSV
GSE271600_NAc-caf-counts.tsv.gz 2.9 Mb (ftp)(http) TSV
GSE271600_NAc-caf-tpm.tsv.gz 13.9 Mb (ftp)(http) TSV
GSE271600_NAc-caf-vsc.tsv.gz 12.7 Mb (ftp)(http) TSV
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