ArticleBiological psychiatry2024
SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens.
Article in Biological psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Nucleus accumbens neuron subtype translatome signatures in socially stressed females.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- GATA3 drives chronic stress-induced depressive-like behaviors by reducing hippocampal CA3 pyramidal neuronal activity in male mice.Acta pharmacologica Sinica · 2026Article
- Review
- A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors.Translational psychiatry · 2026Article
- Glucosylceramide regulates depression through activating peroxisome proliferator-activated receptor gamma in dorsal striatum.Theranostics · 2026Article
- Article
- How dopamine guides our social world.Pharmacological reviews · 2025Review
- Multi-Locus Pro-Dopaminergic Restoration of Reward Brain Circuitry in Reward Deficiency Rescinds Mono-Pharmaceutical Targeting.Neurology (E-Cronicon) · 2025Article
- Alleviation of Microglia Mediating Hippocampal Neuron Impairments and Depression-Related Behaviors by Urolithin B via the SIRT1-FOXO1 Pathway.CNS neuroscience & therapeutics · 2025Article
- Genetic, Epigenetic, and Hormonal Regulation of Stress Phenotypes in Major Depressive Disorder: From Maladaptation to Resilience.Cellular and molecular neurobiology · 2025Review
- Role of sirtuin 1 in depression‑induced coronary heart disease: Molecular pathways and therapeutic potential (Review).Biomedical reports · 2025Review
- Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis.Frontiers in nutrition · 2025Review
- Advances in the prevalence and treatment of depression for adolescents: a review.Frontiers in pharmacology · 2025Review
- Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.Biomarker research · 2024Review
- The nucleus accumbens in reward and aversion processing: insights and implications.Frontiers in behavioral neuroscience · 2024Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMajor depression and anxiety disorders are significant causes of disability and socioeconomic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions. We evaluated the role of SIRT1 in regulating dysfunctional processes of reward by using chronic social defeat stress to induce depression- and anxiety-like behaviors. Chronic social defeat stress induces physiological and behavioral changes that recapitulate depression-like symptomatology and alters gene expression programs in the nucleus accumbens, but cell type-specific changes in this critical structure remain largely unknown.
methodsWe examined transcriptional profiles of D1-expressing medium spiny neurons (MSNs) lacking deacetylase activity of SIRT1 by RNA sequencing in a cell type-specific manner using the RiboTag line of mice. We analyzed differentially expressed genes using gene ontology tools including SynGO and EnrichR and further demonstrated functional changes in D1-MSN-specific SIRT1 knockout (KO) mice using electrophysiological and behavioral measurements.
resultsRNA sequencing revealed altered transcriptional profiles of D1-MSNs lacking functional SIRT1 and showed specific changes in synaptic genes including glutamatergic and GABAergic (gamma-aminobutyric acidergic) receptors in D1-MSNs. These molecular changes may be associated with decreased excitatory and increased inhibitory neural activity in Sirt1 KO D1-MSNs, accompanied by morphological changes. Moreover, the D1-MSN-specific Sirt1 KO mice exhibited proresilient changes in anxiety- and depression-like behaviors.
conclusionsSIRT1 coordinates excitatory and inhibitory synaptic genes to regulate the GABAergic output tone of D1-MSNs. These findings reveal a novel signaling pathway that has potential for the development of innovative treatments for affective disorders.
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