Evidence supporting a mechanistic role of sirtuins in mood and metabolic disorders

Alageel, Asem; Tomasi, Julia; Tersigni, Claudia; Brietzke, Elisa; Zuckerman, Hannah; Subramaniapillai, Mehala; Lee, Yena; Iacobucci, Michelle; Rosenblat, Joshua D.; Mansur, Rodrigo B.; McIntyre, Roger S.

doi:10.1016/j.pnpbp.2018.05.017

Cited by 34 publications

(20 citation statements)

References 67 publications

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“…It has been reported that SIRT1 deacetylates p65 at lysine residue 310 and inhibits the transcriptional activation of NF‐kB, thereby inhibiting the expression of inflammatory cytokines (Xie et al, ; Wang et al, ; Nishida et al, ). SIRT1 links neurodegenerative disease, psychological stress, and depression, and it has been proposed as a novel strategy for treating depression (Alageel et al, ). Recently, the converge (China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology) consortium recruited 11,000 people.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that SIRT1 deacetylates p65 at lysine residue 310 and inhibits the transcriptional activation of NF-kB, thereby inhibiting the expression of inflammatory cytokines Wang et al, 2019;Nishida et al, 2018). SIRT1 links neurodegenerative disease, psychological stress, and depression, and it has been proposed as a novel strategy for treating depression (Alageel et al, 2018).…”

Section: Effect Of Baicalin On Acetylated P65 (At Lysine 310 Site) mentioning

confidence: 99%

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Baicalin reverse depressive‐like behaviors through regulation SIRT1‐NF‐kB signaling pathway in olfactory bulbectomized rats

Zhang

Guan

2019

Phytotherapy Research

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Depression is a common and detrimental illness that affects up to 120 million people worldwide. The present study was designed to evaluate the antidepressant‐like effects and mechanisms of baicalin on olfactory bulbectomized model of depression. Baicalin treatment (20 and 40 mg/kg) significantly reversed the abnormal levels of sucrose consumption, open field test, and forced swimming test. Treatments with baicalin reversed the olfactory bulbectomized‐induced alterations of serum corticosterone levels to a great extent. Our results further demonstrated that baicalin administration negatively regulated the expression of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF‐α) in the hippocampus and hypothalamus. Furthermore, baicalin regulated Sirtuin 1 (SIRT1) and decreased the levels of p65 acetylation (ac‐p65) in the hippocampus and hypothalamus. Moreover, in lipopolysaccharides‐induced BV‐2 cells, the levels of inflammatory factors (IL‐1β), p65 acetylation at lysine 310, and SIRT1 expression were different in the group treated with both baicalin and nicotinamide compared with the group treated with baicalin, which suggests that baicalin regulates SIRT1 and thereby inhibits p65 acetylation. In summary, administration of baicalin reduces the levels of pro‐inflammatory cytokines, possibly through regulation of SIRT1‐NF‐kB pathway. Our findings suggest a support into the potential of baicalin in therapeutic effect for depression.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Baicalin On Acetylated P65 (At Lysine 310 Site) mentioning

confidence: 99%

Baicalin reverse depressive‐like behaviors through regulation SIRT1‐NF‐kB signaling pathway in olfactory bulbectomized rats

Zhang

Guan

2019

Phytotherapy Research

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“…The exact mechanism of the influence of individual sirtuins on the occurrence of mental disorders and neurodegenerative diseases has not yet been clarified (Alageel et al 2018). According to Mendes et al (2017) and Bortell et al (2018), sirtuins 1, 2, 6 and 7 may be of key importance for the regulation of inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Expression of Sir1-Sir7 Genes in the Course of Recurrent Depressive Disorders

Staron¹,

Filip²,

Talarowska³

et al. 2019

Psychiat Danub

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Background: The role of sirtuins as a pathogenetic element of some mental disorders is becoming increasingly more common. They participate in many cellular processes, such as ageing, transcription, apoptosis, inflammatory processes, post-translational modification of proteins, gene transcription silencing, activation of DNA repair mechanisms, and regulation of many metabolic processes. The aim of this paper is to verify the statistical hypothesis assuming the difference in expression at the level of mRNA in genes for sirtuins 1-7 between patients with recurrent depressive disorders (rDD) and patients from the control group, and the hypothesis assuming the relation between the expression at the level of mRNA for these genes and clinical variables in the course of recurrent depressive disorders. Subjects and methods: A total of 198 individuals took part in the study (rDD gropup, N=99; control group, N=99). Results: SIR-1 and SIR-6 expression at the mRNA level was significantly higher among the people with rDD as compared to the subjects from the control group. A reversed relationship was observed for SIR-2, SIR-3, SIR-4 and SIR-5. Statistically significant correlations were observed only in the case of SIR-1 and the number of depression episodes (negative relationship), as well as SIR-5 and the severity of depression measured by the Hamilton Depression Rating Scale (positive relationship). Conclusions: Expression at the mRNA level for selected sirtuins is a factor that significantly differentiates people with depressive episodes from healthy ones. SIR-1 and SIR-6 expression at the mRNA level was significantly higher among the people with depression as compared to the subjects from the control group. A reversed relationship (also statistically significant) was observed for SIR-2, SIR-3, SIR-4 and SIR-5.

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“…Sci. 2020, 21, 295 2 of 15 that sirtuin family gene products catalyze additional reactions and enzymatic activities, including mono-ADP-ribosyltransferase, deacylase, deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activities [2][3][4].Sirtuins are implicated in aging, oxidative stress, maintenance of metabolic homeostasis, DNA repair and mitochondrial function [5,6] through the regulation of specific genes' expression and activation or deactivation of other proteins [7,8].In mammals, seven sirtuin isoforms have so far been described (SIRT1-SIRT7). These possess a conserved catalytic domain but differ in their amino and carboxyl terminal that confers specificity in cellular location and function [9].SIRT1 is the most studied member of the sirtuin family, it is located mainly in the nucleus, although it shuttles to the cytosol in response to environmental signals [10].…”

mentioning

confidence: 99%

“…Sirtuins are implicated in aging, oxidative stress, maintenance of metabolic homeostasis, DNA repair and mitochondrial function [5,6] through the regulation of specific genes' expression and activation or deactivation of other proteins [7,8].…”

mentioning

confidence: 99%

Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

González-Fernández

Martín-Ramírez

Rotoli

et al. 2019

IJMS

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Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We studied gene expression of sirtuins by qRT-PCR in human mural granulosa-lutein cells (hGL) from IVF patients in different infertility diagnostic groups and in oocyte donors (OD; control group). Study 1: sirtuins genes’ expression levels and correlations with age and IVF parameters in women with no ovarian factor. We found significantly higher expression levels of SIRT1, SIRT2 and SIRT5 in patients ≥40 years old than in OD and in women between 27 and 39 years old with tubal or male factor, and no ovarian factor (NOF). Only SIRT2, SIRT5 and SIRT7 expression correlated with age. Study 2: sirtuin genes’ expression in women poor responders (PR), endometriosis (EM) and polycystic ovarian syndrome. Compared to NOF controls, we found higher SIRT2 gene expression in all diagnostic groups while SIRT3, SIRT5, SIRT6 and SIRT7 expression were higher only in PR. Related to clinical parameters SIRT1, SIRT6 and SIRT7 correlate positively with FSH and LH doses administered in EM patients. The number of mature oocytes retrieved in PR is positively correlated with the expression levels of SIRT3, SIRT4 and SIRT5. These data suggest that cellular physiopathology in PR’s follicle may be associated with cumulative DNA damage, indicating that further studies are necessary.

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Evidence supporting a mechanistic role of sirtuins in mood and metabolic disorders

Cited by 34 publications

References 67 publications

Baicalin reverse depressive‐like behaviors through regulation SIRT1‐NF‐kB signaling pathway in olfactory bulbectomized rats

Baicalin reverse depressive‐like behaviors through regulation SIRT1‐NF‐kB signaling pathway in olfactory bulbectomized rats

Expression of Sir1-Sir7 Genes in the Course of Recurrent Depressive Disorders

Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

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