| Autor: |
Mackert S, Niemeyer C, Mecdad Y, Ebert T, Bajaj T, Durand S, Hofer SJ, Zellner A, Besteher B, Engelmann J, Gisabella B, Kempf V, Heckmann LA, Laakmann M, Newman EL, Sokn C, Heinz DE, Junglas E, Uribe-Marino A, Magnes C, Klengel C, Müller A, Opriessnig L, Meinitzer A, Lennarz M, Martin KMW, Albatarni R, Brockherde M, Lieb K, Rohner H, Stoffel-Wagner B, Philipsen A, Kuster B, Kölle M, Ressler KJ, Opel N, Schmidt MV, Pantazopoulos H, Müller MB, Kroemer G, Eisenberg T, Hartmann J, Madeo F, Gassen NC |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Dec 07. Date of Electronic Publication: 2024 Dec 07. |
| DOI: |
10.1101/2024.12.04.626625 |
| Abstrakt: |
Depression is a stress-associated disorder, and it represents a major global health issue. Its pathophysiology is complex and remains insufficiently understood, with current medications often showing limited efficacy and undesirable side effects. Here, we identify imbalanced polyamine levels and dysregulated autophagy as key components of the acute stress response in humans, and as hallmarks of chronic stress and depressive disorders. Moreover, conventional antidepressant pharmacotherapy increases endogenous plasma concentrations of the polyamine spermidine exclusively in patients who respond to the treatment, suggesting a link between spermidine and successful outcomes. In a clinical trial, involving drug-naive depressed individuals, three weeks of spermidine supplementation increased autophagy and alleviated symptoms of depression. Behavioral and mechanistic findings of spermidine supplementation were validated in various mouse stress and depression models. In summary, spermidine supplementation mitigates polyamine dysregulation and stimulates autophagy under pathological stress conditions, offering a novel and well-tolerated treatment approach for stress-related depressive disorders. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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