Suicide and the Polyamine System

Gross, J.; Turecki, Gustavo

doi:10.2174/18715273113129990095

Cited by 32 publications

(22 citation statements)

References 61 publications

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“…In 2010, O'Connor and colleagues reported that chronic immobilization stress altered miR-34c levels in the hippocampus of rats (O'Connor et al, 2012). Of interest, immobilization stress in rats clearly alters brain levels of polyamines, which are generally seen as a stress-response system (Gross, 2013). In our study, we found a significant up-regulation of miR-34c-5p that negatively correlates with the expression of SAT1 in the brain of depressed suicide completers.…”

Section: Discussionsupporting

confidence: 60%

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers

López¹,

Fiori²,

Gross³

et al. 2013

Int. J. Neuropsychopharm.

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MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in the post-transcriptional regulation of mRNA. These molecules have been the subject of growing interest as they are believed to control the regulation of a large number of genes, including those expressed in the brain. Evidence suggests that miRNAs could be involved in the pathogenesis of neuropsychiatric disorders. Alterations in metabolic enzymes of the polyamine system have been reported to play a role in predisposition to suicidal behaviour. We have previously shown the expression of the polyamine genes SAT1 and SMOX to be down-regulated in the brains of suicide completers. In this study, we hypothesized that the dysregulation of these genes in depressed suicide completers could be influenced by miRNA post-transcriptional regulation. Using a stringent target prediction analysis, we identified several miRNAs that target the 3'UTR of SAT1 and SMOX. We profiled the expression of 10 miRNAs in the prefrontal cortex (BA44) of suicide completers (N = 15) and controls (N = 16) using qRT-PCR. We found that several miRNAs showed significant up-regulation in the prefrontal cortex of suicide completers compared to psychiatric healthy controls. Furthermore, we demonstrated a significant correlation between these miRNAs and the expression levels of both SAT1 and SMOX. Our results suggest a relationship between miRNAs and polyamine gene expression in the suicide brain, and postulate a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs.

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Section: Discussionsupporting

confidence: 60%

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers

López¹,

Fiori²,

Gross³

et al. 2013

Int. J. Neuropsychopharm.

Self Cite

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“…Recently, many lines of research have suggested the involvement of the dysregulated polyamine system in suicidal behaviours. 67 , 68 , 69 Surprisingly, we found lower arginase activities (~45% reduction, P <0.01) and a trend of reduced spermidine levels (~25% reduction) in the six suicidal cases when compared with the 14 non-suicidal schizophrenic cases ( Supplementary Figure 1 ). Although the significant positive correlation between arginase activity and the age of disease onset was maintained in the non-suicidal schizophrenic cases, such relationship was not present in the suicidal cases ( Supplementary Figure 1 ).…”

Section: Discussionmentioning

confidence: 70%

Altered brain arginine metabolism in schizophrenia

Liu

Collie

et al. 2016

Transl Psychiatry

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Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

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“…Importantly, the OB efferents are primarily glutamatergic, 40 and olfactory dysfunction would likely disrupt the physiology of OB, which may subsequently contribute to excitatory-inhibitory imbalances in their target regions. In addition, L-ornithine was downregulated, accompanied by the downregulation of the mRNAs encoding Spermidine/spermine N1-acetyltransferase (SAT) and spermine oxidase (SMOX), 41 supporting a disturbance in polyamine catabolism during olfactory dysfunction.…”

Section: Discussionmentioning

confidence: 98%

<p>Commensal Microbiota Regulation of Metabolic Networks During Olfactory Dysfunction in Mice</p>

Wang¹,

Liu²,

Rao³

et al. 2020

NDT

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Introduction: Recently, an increasing number of studies have focused on commensal microbiota. These microorganisms have been suggested to impact human health and disease. However, only a small amount of data exists to support the assessment of the influences that commensal microbiota exert on olfactory function. Methods: We used a buried food pellet test (BFPT) to investigate and compare olfactory functions in adult, male, germ-free (GF) and specific-pathogen-free (SPF) mice, then examined and compared the metabolomic profiles for olfactory bulbs (OBs) isolated from GF and SPF mice to uncover the mechanisms associated with olfactory dysfunction. Results: We found that the absence of commensal microbiota was able to influence olfactory function and the metabolic signatures of OBs, with 38 metabolites presenting significant differences between the two groups. These metabolites were primarily associated with disturbances in glycolysis, the tricarboxylic acid (TCA) cycle, amino acid metabolism, and purine catabolism. Finally, the commensal microbiota regulation of metabolic networks during olfactory dysfunction was identified, based on an integrated analysis of metabolite, protein, and mRNA levels. Conclusion: This study demonstrated that the absence of commensal microbiota may impair olfactory function and disrupt metabolic networks. These findings provide a new entry-point for understanding olfactory-associated disorders and their potential underlying mechanisms.

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Suicide and the Polyamine System

Cited by 32 publications

References 61 publications

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers

Altered brain arginine metabolism in schizophrenia

<p>Commensal Microbiota Regulation of Metabolic Networks During Olfactory Dysfunction in Mice</p>

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