Role and Possible Mechanisms of Sirt1 in Depression

Lu, Guofang; Li, Jianguo; Zhang, Hongmei; Zhao, Xin; Yan, Liang-Jun; Yang, Xiaorong

doi:10.1155/2018/8596903

Cited by 84 publications

(54 citation statements)

References 72 publications

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“…The consequences of SIRT1 activation that we describe here, and those established by others [7][8][9]11,12,14,16,48,67,68 , overlap closely with physiological changes associated with AN pathologies, which supports our hypothesis of AN development (Fig. 4g).…”

Section: Discussionsupporting

confidence: 90%

SIRT1 accelerates the progression of activity-based anorexia

et al. 2020

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Food consumption is fundamental for life, and eating disorders often result in devastating or life-threatening conditions. Anorexia nervosa (AN) is characterized by a persistent restriction of energy intake, leading to lowered body weight, constant fear of gaining weight, and psychological disturbances of body perception. Herein, we demonstrate that SIRT1 inhibition, both genetically and pharmacologically, delays the onset and progression of AN behaviors in activity-based anorexia (ABA) models, while SIRT1 activation accelerates ABA phenotypes. Mechanistically, we suggest that SIRT1 promotes progression of ABA, in part through its interaction with NRF1, leading to suppression of a NMDA receptor subunit Grin2A. Our results suggest that AN may arise from pathological positive feedback loops: voluntary food restriction activates SIRT1, promoting anxiety, hyperactivity, and addiction to starvation, exacerbating the dieting and exercising, thus further activating SIRT1. We propose SIRT1 inhibition can break this cycle and provide a potential therapy for individuals suffering from AN.

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Section: Discussionsupporting

confidence: 90%

SIRT1 accelerates the progression of activity-based anorexia

et al. 2020

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“…It is widely expressed in the CNS and involved in the maintenance of physiological brain functions and exhibits neuroprotective and anti-inflammatory effects in many neurodegenerative diseases. Several studies have shown that SIRT1 deregulation contributes to the pathogenesis of MDD (39, 40). Recent large-scale GWAS studies showed that a SNP close to SIRT1 loci is associated with MDD in Chinese women (41).…”

Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway

et al. 2019

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Inflammation is a crucial component of various stress-induced responses that contributes to the pathogenesis of major depressive disorder (MDD). Depressive-like behavior (DLB) is characterized by decreased mobility and depressive behavior that occurs in systemic infection induced by Lipopolysaccharide (LPS) in experimental animals and is considered as a model of exacerbation of MDD. We assessed the effects of melatonin on behavioral changes and inflammatory cytokine expression in hippocampus of mice in LPS-induced DLB, as well as its effects on NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, oxidative stress and pyroptotic cell death in murine microglia in vitro . Intraperitoneal 5 mg/kg dose of LPS was used to mimic depressive-like behaviors and melatonin was given at a dose of 500 mg/kg for 4 times with 6 h intervals, starting at 2 h before LPS administration. Behavioral assessment was carried out at 24 h post-LPS injection by tail suspension and forced swimming tests. Additionally, hippocampal cytokine and NLRP3 protein levels were estimated. Melatonin increased mobility time of LPS-induced DLB mice and suppressed NLRP3 expression and interleukin-1β (IL-1β) cleavage in the hippocampus. Immunofluorescence staining of hippocampal tissue showed that NLRP3 is mainly expressed in ionized calcium-binding adapter molecule 1 (Iba1) -positive microglia. Our results show that melatonin prevents LPS and Adenosine triphosphate (ATP) induced NLRP3 inflammasome activation in murine microglia in vitro , evidenced by inhibition of NLRP3 expression, Apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, caspase-1 cleavage and interleukin-1β (IL-1β) maturation and secretion. Additionally, melatonin inhibits pyroptosis, production of mitochondrial and cytosolic reactive oxygen species (ROS) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. The beneficial effects of melatonin on NLRP3 inflammasome activation were associated with nuclear factor erythroid 2–related factor 2 (Nrf2) and Silent information regulator 2 homolog 1 (SIRT1) activation, which were reversed by Nrf2 siRNA and SIRT1 inhibitor treatment.

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“…Recent studies suggest that the beneficial effect of antidepressant drugs is mediated via stimulation of adult hippocampal neurogenesis and subsequent increase in hippocampal plasticity. Changes in hippocampal neurons can play an important role in the pathogenesis of depression, involving the possible mechanism of ERK (extracellular signal-regulated kinase) pathway [7], AMPK (Adenosine monophosphate-activated protein kinase) pathway [8], GABAergic dysfunction in the nucleus accumbens (NAc) [9], epigenetic events altering the chromatin structure and thus modulating expression of genes [10], Sirt1 (silent information regulator 1) at the consumption of NAD+ [11], BDNF pathway [12,13], etc. However, mitochondrial energy metabolism in depression remains poorly understood although the action of the above mentioned signalings, at least in part, relies on energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

et al. 2019

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Chronic corticosterone (CORT) stress is an anxiety and depression inducing factor that involves the dysfunction of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and neuronal plasticity. However, the regulation of proteomic profiles in neurons suffering CORT stress is remaining elusive. Thus, the proteomic profiles of mouse neuronal C17.2 stem cells were comprehensively investigated by TMT (tandem mass tag)-labeling quantitative proteomics. The quantitative proteomics conjugated gene ontology analysis revealed the inhibitory effect of CORT on the expression of mitochondrial oxidative phosphorylation-related proteins, which can be antagonized by berberine (BBR) treatment. In addition, animal studies showed that changes in mitochondria by CORT can affect neuropsychiatric activities and disturb the physiological functions of neurons via disordering mitochondrial oxidative phosphorylation. Thus, the mitochondrial energy metabolism can be considered as one of the major mechanism underlying CORT-mediated depression. Since CORT is important for depression after traumatic stress disorder, our study will shed light on the prevention and treatment of depression as well as posttraumatic stress disorder (PTSD).

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Role and Possible Mechanisms of Sirt1 in Depression

Cited by 84 publications

References 72 publications

SIRT1 accelerates the progression of activity-based anorexia

SIRT1 accelerates the progression of activity-based anorexia

Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation

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