Abstract
Prefrontal cortical regions, which are crucial for the regulation of emotionally influenced behaviour, play most probably a dominant role in the pathogenesis of suicide. The study was carried out on paraffin-embedded brain tissue blocks containing specimens from the anterior cingulate cortex (dorsal and ventral parts), the orbitofrontal cortex, and the dorsolateral cortex obtained from 23 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 25 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) as a surrogate marker of protein biosynthesis was evaluated separately in layers III and V pyramidal neurons in regions of interest (ROIs) mentioned above by the AgNOR silver staining method bilaterally. The overall statistical analysis revealed a decrease of AgNOR area suggestive of attenuated rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post-hoc analyses revealed decreases of the median AgNOR area in suicides compared to non-suicides in all 16 ROIs. However, this effect was only significant in the layer V pyramidal neurons of the right ventral anterior cingulate cortex. Our findings suggest that decreased rDNA transcription in prefrontal pyramidal neurons plays possibly an important role in suicide pathogenesis.
Highlights
Disturbances of the prefrontal cortex (PFC) regions, which play a pivotal role in behavioural regulation, are implicated in a multifaceted way in suicidal behaviour (for reviews see: The authors dedicate this work to the memory of Professor Roman Hauser.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.[1, 2])
Nucleolar organising regions (NORs) are genetic loci on chromosomes that are composed of ribosomal DNA and proteins, some of which are argyrophilic
The majority of investigated cases (19 suicide victims and 18 controls, see Supplementary Table 1) revealed a blood alcohol concentration (BAC) below the limit of quantification (LOQ), i.e.
Summary
Disturbances of the prefrontal cortex (PFC) regions, which play a pivotal role in behavioural regulation, are implicated in a multifaceted way in suicidal behaviour The distinctness of suicide in mental disorders has been suggested by our own neuropathological research [4,5,6] (for a review of our previous studies see: [7]). In the AgNOR staining evaluated by light microscopy, AgNORs are indistinguishable from each other and form the AgNOR area. It is located in the nucleolar area but smaller than this area (compared, for instance, with haematoxylin-eosin and Nissl stainings [8]). As a surrogate marker of protein biosynthesis and an important sensor of
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