Advertisement

To Stay Happy, Keep Your SIRT1 Active

      Depression is one of the most common psychiatric disorders and a major cause of disability that affects almost 350 million people worldwide. Common symptoms include depressed mood, persistent anxiety, loss of interest or pleasure in hobbies, feelings of hopelessness, suicidal thoughts, and reduced motivation. Antidepressant drugs often take weeks or even months to reach therapeutic levels and may result in exacerbated symptoms. The pathophysiological cause of depression has not been clearly identified; however, researchers are actively investigating the molecular pathways that contribute to major depressive disorder in human subjects and examining the basis of stress sensitivity and resilience in rodent subjects. One underlying mechanism may be epigenetic, involving the long-lasting regulation of gene expression via histone modification, DNA modification, and chromatin remodeling. Epigenetic enzymes have been linked to various pathophysiological conditions, including depression (
      • Sun H.
      • Kennedy P.J.
      • Nestler E.J.
      Epigenetics of the depressed brain: Role of histone acetylation and methylation.
      ). Sirtuin 1 (SIRT1), a lysine deacetylase, has been extensively studied for its connection to depression, but the specific role of SIRT1 remains controversial. Deciphering the molecular pathways by which SIRT1 may lead to depressed behavior will provide valuable information from a therapeutic perspective.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Sun H.
        • Kennedy P.J.
        • Nestler E.J.
        Epigenetics of the depressed brain: Role of histone acetylation and methylation.
        Neuropsychopharmacology. 2013; 38: 124-137
        • Abe-Higuchi N.
        • Uchida S.
        • Yamagata H.
        • Higuchi F.
        • Hobara T.
        • Hara K.
        • et al.
        Hippocampal sirtuin 1 signaling mediates depression-like behavior.
        Biol Psychiatry. 2016; 80: 815-826
        • Libert S.
        • Pointer K.
        • Bell E.L.
        • Das A.
        • Cohen D.E.
        • Asara J.M.
        • et al.
        SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive.
        Cell. 2011; 147: 1459-1472
        • Ferland C.L.
        • Schrader L.A.
        Regulation of histone acetylation in the hippocampus of chronically stressed rats: A potential role of sirtuins.
        Neuroscience. 2011; 174: 104-114
        • Ng F.
        • Wijaya L.
        • Tang B.L.
        SIRT1 in the brain-connections with aging-associated disorders and lifespan.
        Front Cell Neurosci. 2015; 9: 64
        • Li J.Z.
        • Bunney B.G.
        • Meng F.
        • Hagenauer M.H.
        • Walsh D.M.
        • Vawter M.P.
        • et al.
        Circadian patterns of gene expression in the human brain and disruption in major depressive disorder.
        Proc Natl Acad Sci U S A. 2013; 110: 9950-9955
        • Gao J.
        • Wang W.Y.
        • Mao Y.W.
        • Graff J.
        • Guan J.S.
        • Pan L.
        • et al.
        A novel pathway regulates memory and plasticity via SIRT1 and miR-134.
        Nature. 2010; 466: 1105-1109
        • Michan S.
        • Li Y.
        • Chou M.M.
        • Parrella E.
        • Ge H.
        • Long J.M.
        • et al.
        SIRT1 is essential for normal cognitive function and synaptic plasticity.
        J Neurosci. 2010; 30: 9695-9707
        • Qiao H.
        • Li M.X.
        • Xu C.
        • Chen H.B.
        • An S.C.
        • Ma X.M.
        Dendritic spines in depression: What we learned from animal models.
        Neural Plast. 2016; 2016: 8056370
        • Li Y.
        • Xu W.
        • McBurney M.W.
        • Longo V.D.
        SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons.
        Cell Metab. 2008; 8: 38-48

      Linked Article

      • Hippocampal Sirtuin 1 Signaling Mediates Depression-like Behavior
        Biological PsychiatryVol. 80Issue 11
        • Preview
          Although depression is the leading cause of disability worldwide, its pathophysiology is poorly understood. Recent evidence has suggested that sirtuins (SIRTs) play a key role in cognition and synaptic plasticity, yet their role in mood regulation remains controversial. Here, we aimed to investigate whether SIRT function is associated with chronic stress-elicited depression-like behaviors and neuronal atrophy.
        • Full-Text
        • PDF