Evidence of altered polyamine concentrations in cerebral cortex of suicide completers

Abstract

Recent studies have implicated alterations in the expression of polyamine-related genes in the brains of suicide completers including widespread downregulation of spermidine/spermine N1-acetyltransferase, the key enzyme in polyamine catabolism, suggesting compensatory mechanisms attempting to increase brain levels of polyamines. Given the complexity of the polyamine system, quantification of the levels of the polyamines is an essential step in understanding the downstream effects of dysregulated gene expression. We developed a method using high-resolution capillary gas chromatography (GC) in combination with mass spectrometry (MS) for quantitation of polyamines from post-mortem brain tissue, which allowed us to accurately measure spermidine and putrescine concentrations in post-mortem brain tissues. Using this method, we analyzed putrescine and spermidine levels in a total of 126 samples from Brodmann areas 4, 8/9, and 11, from 42 subjects, comprising 16 suicide completers with major depression, 13 non-depressed suicide completers, and 13 control subjects. Both putrescine and spermidine levels fell within the expected nanomolar ranges and were significantly elevated in the brain of suicide completers with a history of major depression as compared with controls. These results were not accounted by possible confounders. This is the first GC-MS study to analyze the expression of putrescine and spermidine from post-mortem brain tissue and confirms the hypothesis raised by previous studies indicating alterations in putrescine and spermidine levels in suicide/major depression.

Figure 1

GC–MS spectra of polyamines and internal standards. (a) Total ion current (TIC) chromatogram for the derivatives of the authentic amines, putrescine, and spermidine, as well as the internal standard diaminoheptane, used in the study. (b, c) Composite selected ion chromatograms (SIM) for putrescine, spermidine, and the internal standard diaminoheptane isolated from the cortex of a suicide completer (b) and a control subject (c).

Figure 2

(a) Putrescine and (b) spermidine levels in post-mortem brain tissues. Concentrations (ng/mg tissue)+SEM were obtained from controls (C), suicide completers without major depressive disorder (NDS), and suicide completers with major depressive disorder (SMD). ^*P⩽0.05; ^**P⩽0.01.