Evidence of Reduced Agmatine Concentrations in the Cerebral Cortex of Suicides.
|Title||Evidence of Reduced Agmatine Concentrations in the Cerebral Cortex of Suicides.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Chen GG, Almeida D, Fiori L, Turecki G|
|Journal||Int J Neuropsychopharmacol|
|Date Published||2018 Jul 09|
Background: The polyamines are a group of ubiquitous low molecular weight aliphatic molecules that play an essential role in various physiological functions of the mammalian CNS. Previous literature has indicated alterations in the expression of polyamine-related genes in the brains of individuals who died by suicide; including downregulation of spermidine/spermine N1-acetyltransferase (SAT1), a key enzyme involved in polyamine catabolism. One such polyamine, namely agmatine, has been shown to act as an anti-depressant in animal models of depressive-like behaviour. Yet, agmatine concentrations have not been explored in postmortem human brain of suicides.Methods: In order to measure agmatine in post-mortem human brain tissue, we employed our previously published high-resolution capillary gas chromatography (GC) in combination with mass spectrometry (MS) method. Using this method, we analyzed agmatine levels in a total of 120 tissue samples from Brodmann areas 4, 11, and 44 of 40 male subjects comprising controls (N=13), individuals who died by suicide and met criteria for major depressive disorder (MDD) (N=14) and subjects who died by suicide and did not meet criteria for MDD (N=13).Results: Agmatine fell within the expected nanomolar range and was significantly reduced in the cortex of suicides, irrespective of meeting criteria for MDD, as compared with controls.Conclusions: This is the first GC-MS study to analyze agmatine concentrations in human post-mortem brain of suicides. These results add to our mechanistic understanding of the role that the polyamine stress response pathway may play in the neurobiology of major depression and/or suicide.
|Alternate Journal||Int. J. Neuropsychopharmacol.|