SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens.
Hee-Dae KimJennifer HestermanTanessa CallSamantha MagazuElizabeth KeeleyKristyna ArmentaHope KronmanRachael L NeveEric J NestlerDeveroux FergusonPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
In this study, we demonstrate a pivotal role for SIRT1 in anxiety- and depression-like behaviors in the nucleus accumbens (NAc), a key brain reward region. We show that stress stably induces SIRT1 expression in this brain region and that altering SIRT1 activity using a pharmacological or genetic approach regulates anxiety- and depression-like behaviors. These results suggest that SIRT1 plays an essential role in regulating mood-related behaviors and introduces a novel signaling pathway for the development of innovative antidepressants to treat depression and other stress-related disorders. A recent groundbreaking publication by the CONVERGE Consortium (2015) identified a reproducible association of the SIRT1 locus with major depression in humans. Therefore, our results are timely and have significant translational relevance.
Keyphrases
- oxidative stress
- ischemia reperfusion injury
- signaling pathway
- depressive symptoms
- poor prognosis
- resting state
- white matter
- transcription factor
- epithelial mesenchymal transition
- major depressive disorder
- genome wide
- functional connectivity
- copy number
- induced apoptosis
- endoplasmic reticulum stress
- prefrontal cortex