| Autor: |
Stein, Gregor, Aly, Janine S., Lange, Lisa, Manzolillo, Annamaria, Riege, Konstantin, Brancato, Anna, Hübner, Christian A., Turecki, Gustavo, Hoffmann, Steve, Engmann, Olivia |
| Zdroj: |
Molecular Psychiatry; 20240101, Issue: Preprints p1-8, 8p |
| 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. Npbwr1is 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 Bdnflevels. 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. |
| Databáze: |
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