The changes in AgNOR parameters of dorsal raphe nucleus neurons are related to suicide
Introduction
Suicide, which causes almost half of all violent deaths and results in nearly one million fatalities in the world every year, is rapidly becoming a public health problem of great magnitude. Studies from both developing and developed countries reveal an overall prevalence of mental disorders of 80–100% in cases of completed suicide and what is more, depression is most common among them [1]. Considering the recent neurobiological evidences, depression and suicide are distinct phenomena although share similarities and the unequivocally distinguishing diagnostic criteria have not yet been established [2], [3], [4], [5], [6]. They could be also important for the postmortem diagnostics of unclear forensic cases.
The disturbed serotonin neurotransmitter system is implicated in the etiology of depression, aggression, impulsivity and suicide [5], [7], [8], [9], [10], [11], [12], [13]. About 70% of neurons within the boundaries of the dorsal raphe nucleus (DRN) are serotonergic [14] and nearly all the large cells with long projecting fibers in this nucleus are serotonergic [15]. They provide the majority of serotonergic innervation to the medial prefrontal cortex and the nucleus accumbens which are key structures for the regulation of emotionally influenced behavior [14], [16], [17], [18]. A number of studies revealed biochemical and morphological changes in the DRN in suicide victims [6], [19], [20], [21], [22], [23], [24].
Nucleolar organizer (NOR) is the active region of nucleus, in which most of ribosomal synthesis occurs. NOR is composed of ribosomal DNA (rDNA) and proteins, some of which are argyrophilic. Argyrophilic nucleolar organizer (AgNOR) represents the site of ribosomal RNA synthesis and transcriptionally active NOR and is synonymous with the nucleolar area. Therefore, the cellular activity in terms of transcriptional activity of rDNA can be evaluated by measuring AgNOR [25], [26], [27], [28], [29], [30]. The relatively simple AgNOR staining method is well established in neuropathology [31], [32], [33], [34], [35], [36] and has been used both in forensic research and practice yet [35], [37]. The usefulness of AgNOR parameters in postmortem research has been proved in human brain [6], [38]. Recently, the AgNOR method has been applied to depression and suicide research [6] which could be also relevant for the forensic diagnostics.
Section snippets
Subject characteristics
Brains were collected postmortem from 10 patients with mood disorders (5 women, 5 men). The age range was 26–69 years. Of these, five subjects died by suicide, including 3 women and 2 men, ranging in age from 26 to 59 years. The methods of suicide were hanging (2), overdose of medication (1), incision of radial artery (1) and fall from the height (1). The determination of suicide was made by the Medical Examiner and verified by the investigators based on the individual records. The remaining
Results
After silver staining of DRN neurons, AgNOR (synonymous with the nucleolus) and nuclear borders are clearly visible within DRN neurons (Fig. 1). Most of the neurons contained one AgNOR; whereas, two or more AgNORs were observed very seldom.
The cumulative analysis of all DRN subnuclei was more informative than of particular subregions. The Kruskal–Wallis test revealed in this analysis a significant effect of suicide as a single factor on the mean values of nuclear area and AgNOR-ratio (P-values
Discussion
The present study revealed a significantly reduced nuclear area of DRN neurons paralleled by non-significantly reduced AgNOR area and number of depressive suicides vs non-suicides and controls. As regards the difference between suicides and other depressives, the results are consistent with those reported initially in DRN also on a small sample of cases [6]. However, this difference should be approached cautiously because of the unbalanced diagnostic composition (unipolar vs bipolar cases) of
Acknowledgments
The work described here was supported by grants of the Stanley Foundation, the Deutsche Forschungsgemeinschaft (DFG 799/6-1), the Bundesministerium für Bildung und Forschung (BMBF NBL-3/2 and 01ZZ0407) and the Alfried-Krupp-von-Bohlen-und-Halbach Stiftung.
We thank S. Funke and H. Dobrowolny for the excellent technical assistance.
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Decreased ribosomal DNA transcription in dorsal raphe nucleus neurons is specific for suicide regardless of psychiatric diagnosis
2016, Psychiatry ResearchCitation Excerpt :Hence, the evaluation of DRN pathology in suicide should be continued. Previously we have hypothesized that the decreased transcriptional activity of ribosomal DNA (rDNA) in DRN neurons in suicide could represent a diagnosis-overreaching phenomenon of possible relevance in forensic differential diagnostics between suicidal and non-suicidal death in unclear cases (Gos et al., 2007, 2008). Our recent study of forensic cases with unknown psychiatric diagnoses has supported this hypothesis (Krzyżanowska et al., 2016), which corresponds with numerous research data on serotonergic hypofunction in suicide (for reviews see: Ernst et al., 2009; Bach and Arango, 2012; Mann, 2013).
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