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Opioid addiction is a worldwide problem accentuated in the USA and European countries by the COVID-19 pandemic. The nucleus accumbens (NAc) plays an outstanding neurobiological role in opioid addiction as a part of the striatum and key component of brain reward system. The striatal GABAergic medium spiny projection neurons (MSNs) are the main neuronal type in the NAc where addiction-specific synaptic plasticity occurs. The activity of ribosomal DNA (rDNA) transcription is crucial for neural plasticity and molecular studies suggest its increase in the NAc of heroin addicts. Silver-stained argyrophilic nucleolar organizer region (AgNOR) areas visualised in neuronal nuclei in paraffin-embedded brain sections are reliable morphological estimators of rDNA transcription and thus surrogate markers for the activity of brain regions. Our study revealed increased AgNOR areas in MSNs of the left NAc in 11 heroin addicts versus 11 healthy controls from the Magdeburg Brain Bank (U-test P = 0.007). No differences were observed in another investigated part of the striatum, namely the head of caudate nucleus, which is located closely to the NAc. The results were not confounded by significant differences in the age, brain volume and time of formalin fixation existing between compared groups. Our findings suggest an increased NAc activity in heroin addicts, which is consistent with human and animal experimental data. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The karyotypes of three species of social voles recently discovered in Turkey (Microtus irani karamani, M. schidlovskii, and M. anatolicus) were investigated. All specimens examined revealed similar karyotypes comprising 60 chromosomes in the diploid complement. All autosomes and the X chromosome were acrocentric. The subtelocentric Y chromosome was recorded in M. anatolicus but it was acrocentric in the other species. Dark C-bands were observed in centromeric/pericentromeric areas of all the acrocentric autosomes. The X chromosome had a centromeric C-positive area and the Y chromosome was completely heterochromatic in all specimens examined. AgNORs were recorded in the pericentromeric region of seven autosome pairs in M. irani karamani, ten autosome pairs in M. schidlovskii, and eight autosome pairs of M. anatolicus. Differences in the NOR distribution between the species were quantified in a neighbor-joining tree. The individuals of M. anatolicus appeared as the basal branch in relation to the derived sister group of M. schidlovskii and M. irani karamani. [ABSTRACT FROM AUTHOR]

The variation pattern of the C-heterochromatin and nucleolar organizer region (nOr) distribution, both between and within two cytotypes of M. arvalis with 46 chromosomes, are described. The positive C-bands were observed on six or seven small bi-armed autosomal pairs and in two, three or four acrocentric autosomal pairs. Only a small dark C-band was observed in the acrocentric homologue from a large heteromorphic autosomal pair in the complement of specimens belonging to the obscurus cytotype. The nucleolar organizer region was localized in the secondary constrictions in three autosomal pair in the specimens of the obscurus cytotype. These results may contribute to the knowledge of cytogenetic differentiation between the cytotypes and investigation of their systematic status.

Background and Objectives: Nucleolar organizer Regions (NORs) are situated within the nucleolus of a cell. The proteins are selectively stained by the silver colloid technique that is known as the AgNOR technique. AgNOR stain can be visualized as a black dot under the optical microscope. The present study aimed to evaluate the cases for quantitative estimation of AgNORs in the epithelial cells in various grades of gingival overgrowth to that of normal gingival tissues. Materials and Methods: Only preadolescent and adolescent groups aged up to 14 years were selected. Twenty normal and 31 disease cases of gingival overgrowth were selected. The tissue sections were stained by the hematoxylin and eosin (HandE) technique for the routine histological evaluation, while the AgNOR counts were performed through the improved one-step method of Ploton et al. Results: HandE staining revealed five different types of gingival overgrowth. The plaque index (PI), gingival index (GI), and AgNOR count were not significantly (P> 0.05) higher than that of control cases in pyogenic granuloma, puberty gingivitis, and in drug-induced gingival overgrowth cases. In gingival fibromatosis cases, for comparison of different indices t-tests were done. The PI when compared with AgNOR count was found significant at 5% level and 0.1% level for mixed and permanent dentition, respectively. The GI when compared with AgNOR count was found significant at 1% level and 0.1% level in mixed and permanent dentitions, respectively.

The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour. We have evaluated the transcriptional activity of ribosomal DNA (rDNA) in DRN neurons by AgNOR silver staining method. The cohort (containing 24 suicidal and 20 non-suicidal patients, and 28 controls) was previously analysed regarding diagnosis-related differences between schizophrenia and affective disorders. Significant decreases in both AgNOR and nuclear areas suggestive of attenuated rDNA activity were currently found in suicidal versus non-suicidal patients. This effect, which was more accentuated in affective disorders patients, was not explained by antidepressant and antipsychotic medication. [ABSTRACT FROM AUTHOR]

An involvement of the central serotonergic system has been implicated in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour. The study was carried out on paraffin-embedded brainstem blocks containing the DRN obtained from 27 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 30 non-suicidal controls. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons as a surrogate marker of protein biosynthesis was evaluated by the AgNOR silver staining method. Significant decreases in AgNOR parameters suggestive of attenuated rDNA activity were found in the cumulative analysis of all DRN subnuclei in suicide victims versus controls ( U test P values < 0.00001). Our findings suggest that the decreased activity of rDNA transcription in DRN neurons plays an important role in suicide pathogenesis. The method accuracy represented by the area under receiver operating characteristic curve (>80 %) suggests a diagnostic value of the observed effect. However, the possible application of the method in forensic differentiation diagnostics between suicidal and non-suicidal death needs further research. [ABSTRACT FROM AUTHOR]

The karyotypes of Dryomys laniger and D. nitedula from Turkey were studied using C-banding and AgNOR staining. The standard karyotypes found in both species were fairly similar to previously published data (2n = 46, NF = 92 in D. laniger; 2n = 48, NF = 96 in D. nitedula). The C-banding pattern revealed a relatively small amount of heterochromatin in both karyotypes and C-heterochromatin was concentrated at centromeric areas of most autosomes and the X chromosome. Heterochromatin changes have apparently not been responsible for karyotypic divergences between the studied species. The AgNORs were recorded in the pericentromeric region of two autosome pairs in the complement of D. laniger, and at a single autosome pair of D. nitedula. The complement of D. laniger could be derived from that of D. nitedula after a tandem fusion of two autosomal pairs, and the assumed rearrangement also included the NOR region. [ABSTRACT FROM AUTHOR]

The central serotonergic system is implicated differentially in the pathogenesis of depression and schizophrenia. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in both disorders. The study was carried out on paraffin-embedded brains from 27 depressed (15 major depressive disorder, MDD and 12 bipolar disorder, BD) and 17 schizophrenia (9 residual and 8 paranoid) patients and 28 matched controls without mental disorders. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons was evaluated by the AgNOR silver staining method. A significant effect of diagnosis on rDNA activity was found in the cumulative analysis of all DRN subnuclei. Further analysis revealed an increase in this activity in residual (but not paranoid) schizophrenia compared to depressed (both MDD and BD) patients. The effect was most probably neither confounded by suicide nor related to antidepressant and antipsychotic medication. Our findings suggest that increased activity of rDNA in DRN neurons is a distinct phenomenon in residual schizophrenia, related presumably to differentially disturbed inputs to the DRN and/or their local transformation compared with depressive episodes in patients with affective disorders. [ABSTRACT FROM AUTHOR]

Background and Aim: A strong causal relationship exists between cigarette smoking and development of oral squamous cell carcinoma, so oral screening using exfoliative cytology has been recommended to facilitate the early diagnosis of cellular alterations in oral mucosa and silver staining (AgNOR technique) has been proven to be of value in the detection of incipient cellular alterations. The purpose of this study was to compare the argyrophilic nucleolar regions (AgNORs) count of cells collected from normal mucosa of cigarette smokers with that obtained from non- smokers. Materials and Methods: In this cross-sectional study, cytologic smears of normal tongue, buccal mucosa and floor of the mouth from 19 smokers and 19 non- smokers were stained for AgNORs. The AgNORs count was established on 100 cells. The count value of groups were compared and analyzed using the Levens, Paired T, Student and Factorial tests. Using P

Nucleolar alterations resulting from the action of either chemical or physical agents can serve as important genotoxicity biomarkers. In this study, the efficiency of AgNOR banding technique to identify the presence of nucleoli in micronucleus and assess nucleolar alterations in aberrant cells of Allium cepa was evaluated. Seeds of this plant were exposed to both water samples from a river that receives untreated urban effluent and to the trifluralin herbicide (0.84 mg/L concentration), both analyzed in two different seasons (summer and winter seasons). Samples induced significant frequencies of chromosomal and nuclear aberrations and micronuclei, as observed in cells submitted to conventional chromosomal staining. The herbicide caused a significant increase in the number of nucleoli and micronuclei, interpreted as due to the elimination of excessive nucleolar material resulting from polyploidization. The use of the AgNOR technique enabled the identification of both the presence of the nucleolus in some micronuclei and the nucleolar organizer region (NOR) behavior of aberrant cells. The NOR-banding technique showed to be an efficient tool for studying the genotoxic effects caused by a xenobiotics and a complex environmental sample. [ABSTRACT FROM AUTHOR]

The central serotonergic system is implicated in the pathogenesis of schizophrenia, where the imbalance between dopamine, serotonin and glutamate plays a key pathophysiological role. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in schizophrenia patients. The study was carried out on paraffin-embedded brains from 17 (8 paranoid and 9 residual) schizophrenia patients and 28 matched controls without mental disorders. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons was evaluated by the AgNOR silver-staining method. An increased rDNA transcriptional activity was found in schizophrenia patients in the cumulative analysis of all DRN subnuclei ( t test, P = 0.02). Further subgroup analysis revealed that it was an effect specific for residual schizophrenia versus paranoid schizophrenia or control groups (ANOVA, P = 0.002). This effect was confounded neither by suicide nor by antipsychotic medication. Our findings suggest that increased activity of rDNA in DRN neurons is a distinct phenomenon in schizophrenia, particularly in residual patients. An activation of the rDNA transcription in DRN neurons may represent a compensatory mechanism to overcome the previously described prefrontal serotonergic hypofunction in this diagnostic subgroup. [ABSTRACT FROM AUTHOR]

Abstract: The anterior cingulate cortex (AC) is consistently implicated in the pathophysiology of depression. However, it is not clear whether unipolar and bipolar depression display distinct neuropathological features. Therefore, the objective of this post-mortem study was to re-evaluate this important issue. Brains from 9 patients with major depressive disorder (MDD) and 11 patients with bipolar disorder (BD) subtype I depression as well as 24 matched controls were analysed. The argyrophilic nucleolar organiser region (AgNOR) silver-staining method was applied on paraffin-embedded brain sections in order to assess the transcriptional activity of ribosomal DNA (rDNA) in layer III and V pyramidal neurons of the dorsal and ventral AC in both hemispheres. An AgNOR area decrease suggestive of a diminished transcriptional activity of rDNA was found in the MDD group both versus controls and versus the BD group. The effect was specific for the right hemisphere and dorsal AC and was restricted to layer V pyramidal neurons. The results suggest that only patients with MDD display region-specific chronic hypoactivity of these output neurons, which are critical for mood regulation. Furthermore, in our cohort, unipolar and bipolar I depression could be differentiated relative to the presumed AC hypoactivity and psychotropic medication did not counteract the observed effect. [Copyright &y& Elsevier]

A chromosomal study of Allactaga euphratica from the Şanlıurfa Province in Southeast Anatolia, Turkey, was performed. The diploid number of 48 chromosomes was found in all four specimens examined. The C-band-positive regions were distributed in centromeric areas of all the autosomal pairs and the X chromosome. Extensive C-positive heterochromatin intercalary blocks were observed in the largest pair of autosomes. The small Y chromosome was stained uniformly and C-negatively. The active nucleolus organizer regions (NORs) were localized in two pairs of small bi-armed autosomes. The C-heterochromatin distribution and localization of the secondary constrictions bearing NORs apparently differ between karyotypes of the related jerboa species A. euphratica and Allactaga williamsi. This cytogenetic difference may be implied as a suitable marker in further studies of the relationships in contact zones and possible hybridization between these two taxa. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim to find a morphological biomarker of disturbed activity of the lateral amygdaloid nucleus in depression was approached by a karyometric analysis of projection neurons. Methods: The study was performed on paraffin-embedded brains from 19 depressed patients from both the major depressive disorder (MDD) and the bipolar disorder (BD) diagnostic groups, including 10 suicides, and 24 matched controls. The karyometric parameters of the lateral amygdaloid nucleus (La) projection neurons bilaterally were evaluated by the argyrophilic nucleolar organiser region (AgNOR) silver staining method. Results: An increased AgNOR number was found in the right La in suicides compared to controls. The intra-group comparisons between the hemispheres suggest a disturbed amygdaloid lateralisation in depressed patients. The effects were independent from psychotropic medication. There was a strong positive correlation between the nuclear area in La projection neurons and prefrontal limbic areas pyramidal neurons in the right hemisphere specific for suicide and MDD. Limitations: A major limitation of this study is the relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the entire lifespan. Conclusion: The results suggest that depressed patients from both the MDD and BD diagnostic groups exhibit an increased activity of the La output neurons specific for suicidal patients. The distinctness of the diagnostic groups of mood disorders was accentuated in the correlation analysis. This putative hyperactivity was specific for the right hemisphere and psychotropic medication most likely did not counteract it. [ABSTRACT FROM AUTHOR]

Abstract: Background: The external globus pallidus (EGP) is thought to play the most important integrating and conveying role in the striatopallidal system involved in the transfer from motivation to action. The aim to find a morphological biomarker of disturbed EGP activity in depression was approached by the karyometric analysis of large projecting neurons. Methods: The study was performed on paraffin-embedded brains from 19 depressed patients from both the major depressive disorder (MDD) and the bipolar disorder (BD) diagnostic groups encompassing 10 suicides and from 24 controls. The karyometric parameters of EGP neurons bilaterally were evaluated by argyrophilic nucleolar organiser (AgNOR) silver staining method. Results: A significantly decreased AgNOR area was found in the left EGP neurons in depressed patients compared to controls. The distinctness of the diagnostic groups and suicidal vs non-suicidal patients was not shown in the statistical comparisons. The AgNOR parameter which was decreased correlated positively with the mean dose of benzodiazepines in non-suicidal patients. Limitations: A major limitation of this study is the relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the whole lifespan of patients. Conclusion: The results suggest disturbed, most likely decreased, activity of the left EGP projecting neurons in depressed patients, a disturbed activity that should hypothetically be counteracted by the applied pharmacotherapy in non-suicidal patients. [Copyright &y& Elsevier]

Abstract: Background: The aim to find the morphological biomarker of disturbed activity of the orbitofrontal cortex (OFC) in depression was approached by the karyometric analysis of pyramidal neurons. Methods: The study was performed on paraffin-embedded brains from 19 depressed patients from both major depressive disorder (MDD) and bipolar disorder (BD) diagnostic groups, including 9 suicides, and 24 matched controls. The karyometric parameters of medial OFC layer III and V pyramidal neurons bilaterally were evaluated by argyrophilic nucleolar organiser region (AgNOR) silver staining method. Results: The enlarged nuclear area was found in layer V pyramidal neurons in the right OFC in non-suicides compared to suicides and controls, which was most likely the effect of neuroleptics. The intra-group comparisons between the hemispheres suggest the disturbed orbitofrontal lateralisation in depressed patients (predominantly in suicides) with moderate distinctness of the MDD and the BD diagnostic groups. Limitations: A major limitation of this study is a relatively small number of cases. A further limitation is given by the lack of data on drug exposure across the whole lifespan. Conclusion: The results suggest disturbed activity of OFC pyramidal neurons in depression, distinct in suicide and the diagnostic groups of mood disorders. The non-suicidal patients seem to benefit from neuroleptics, which most likely increase the activity of the subpopulation of OFC pyramidal neurons. [Copyright &y& Elsevier]

Abstract: Background: Suicide and depression are closely related yet distinct phenomena. In both these phenomena, research has focused on central serotonergic system disturbances. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of limbic structures crucial for the regulation of emotionally influenced behaviour. Methods: The study was carried out on paraffin-embedded brains from 23 depressed patients (12 suicides and 11 non-suicides) and 26 matched controls without mental disorders. The karyometric parameters of DRN neurons were evaluated by the AgNOR silver staining method. Results: The significant effect of suicide on the nuclear area was found in the cumulative analysis of all DRN subnuclei (ANOVA, P =0.032). A decreased mean value of this parameter was observed in the suicides group versus controls (t-test, P =0.032). This effect was especially pronounced in the violent suicide victims (t-test, P =0.001), who also demonstrated a decreased AgNOR area versus controls (t-test, P =0.007). No significant effect of depression or polarity on AgNOR parameters was found. Limitations: A major limitation of this study is relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. Conclusion: Our findings suggest that hypoactivity of DRN neurons is a distinct phenomenon in depression, specific only for suicidal subgroup of depressed patients. [Copyright &y& Elsevier]

The anterior cingulate cortex (AC) is consistently implicated in the pathophysiology of depression. While suicide has been shown in previous reports to be closely related to depression, it is still a distinct phenomenon. The aim to differentiate between depression and suicide was approached by the karyometric analysis of AC pyramidal neurons. The study was performed on paraffin-embedded brains from 20 depressive patients (10 of whom had committed suicide) and 24 matched controls. The karyometric parameters of the layer III and V pyramidal neurons of the dorsal and ventral AC were evaluated bilaterally by Argyrophilic Nucleolar Organiser (AgNOR) silver staining method. Control-specific was the increased nuclear area in ontogenetically younger pyramidal neurons layer III in the left dorsal compared with ventral AC (Wilcoxon test, P<0.01). The decreased AgNOR number per nucleus in these cells in the right ventral AC was depression-specific compared with controls (t-test, P=0.047). On the other hand, the diffuse decrease in AgNOR ratio throughout pyramidal neurons on the left side was specific for suicidal depressive patients compared with non-suicidal patients and controls (ANOVA, P=0.028). The results suggest that regionally differentiated depression- and suicide-specific disturbed function of the most important AC output cells exists in depressive patients. [ABSTRACT FROM AUTHOR]

Abstract: Depression has been established as the main cause of suicide and the research has concentrated on disturbed central serotonergic system in both disorders. The dorsal raphe nucleus (DRN) of brain stem is the main source of serotonergic innervation of limbic structures fundamental in the regulation of emotionally influenced behavior. The study was carried out on paraffin-embedded brains from 10 depressive patients, among them 5 suicides and 5 non-suicides and 13 matched mentally healthy controls. The karyometric parameters of DRN neurons were evaluated by AgNOR (Argyrophilic Nucleolar Organizer) silver staining method. The significant effect of suicide on nuclear area and AgNOR-ratio found in the cumulative analysis of all DRN subnuclei could be relevant for forensic diagnostic. The results suggest DRN neurons hypoactivity specific for suicide. Whether observed phenomenon is a “common trait” existing also in other diagnostic groups of mental disorders remains an open question. [Copyright &y& Elsevier]

A proliferative activity study analysing morphometric and quantitative aspects of nucleolar organizer regions (NORs) and proliferating cell nuclear antigen (PCNA) expression was conducted in 10 cases of peripheral ossifying fibroma (POF) and 10 cases of ossifying fibroma (OF). For NOR identification, the silver staining technique (AgNOR technique) was used. PCNA expression was determined by immunohistochemical staining using the PC10 antibody. The AgNOR analysis for the two lesions showed a profile characteristic of benign lesions. OF showed higher AgNOR number and PCNA expression than POF. Our results suggest increased proliferative activity in OF compared with POF. [ABSTRACT FROM AUTHOR]

Nine cases of adenoid cystic carcinomas (ACC) and three cases of polymorphous low-grade adenocarcinomas (PLGA) of the salivary glands from the Surgical Oral Pathology Service of the University of Sao Paulo School of Dentistry were examined by menas of the silver-staining nucleolar organizer regions (AgNOR) technique. Quantitative and dimensional analyses of NORs were carried out. Our findings suggest that solid and cribriform patterns of ACC have a higher cellular activity than that presented by tubular ACC and PLGA. [ABSTRACT FROM AUTHOR]