Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles (Data Paper) Neuropsychopharmacology Year : 2017

Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors


Depression is a leading cause of disease burden, yet current therapies fully treat o50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here we examined a possible role for the DNA dioxygenase, ten-eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region. We show decreased Tet1 expression in NAc in stress-susceptible mice only. Surprisingly, selective knockout of Tet1 in NAc neurons of adult mice produced antidepressant-like effects in several behavioral assays. To identify Tet1 targets that mediate these actions, we performed RNAseq on NAc after conditional deletion of Tet1 and found that immune-related genes are the most highly dysregulated. Moreover, many of these genes are also upregulated in the NAc of resilient mice after chronic social defeat stress. These findings reveal a novel role for TET1, an enzyme important for DNA hydroxymethylation, in the brain's reward circuitry in modulating stress responses in mice. We also identify a subset of genes that are regulated by TET1 in this circuitry. These findings provide new insight into the pathophysiology of depression, which can aid in future antidepressant drug discovery efforts.


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Dates and versions

inserm-03949688 , version 1 (20-01-2023)



Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, et al.. Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Neuropsychopharmacology, 2017, 42 (8), pp.1657-1669. ⟨10.1038/npp.2017.6⟩. ⟨inserm-03949688⟩


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