Npbwr1 signaling mediates fast antidepressant action.

Autor: Stein G; Institute for Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany., Aly JS; Institute of Human Genetics, Jena University Hospital, Am Klinikum 1, F2E20, 07747, Jena, Germany., Lange L; Institute for Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany., Manzolillo A; Institute of Human Genetics, Jena University Hospital, Am Klinikum 1, F2E20, 07747, Jena, Germany., Riege K; Computational Biology Group, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745, Jena, Germany., Brancato A; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Hübner CA; Institute of Human Genetics, Jena University Hospital, Am Klinikum 1, F2E20, 07747, Jena, Germany., Turecki G; Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada., Hoffmann S; Computational Biology Group, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745, Jena, Germany., Engmann O; Institute for Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany. olivia.engmann@uni-jena.de.; Institute of Human Genetics, Jena University Hospital, Am Klinikum 1, F2E20, 07747, Jena, Germany. olivia.engmann@uni-jena.de.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Oct 21. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1038/s41380-024-02790-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: