Altered chromatin ultrastructure in neutrophils of schizophrenics

Issidorides, Marietta R.; Stefanis, Costas N.; Varsou, Eleftheria; Katsorchis, Theodoros

doi:10.1038/258612a0

Cited by 42 publications

(26 citation statements)

References 14 publications

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“…Almost four decades ago, an alteration of chromatin ultrastructure and an increase in arginine-rich histones were reported in the neutrophils of SCZ patients that could be attenuated by pimozide, a DRD2 antagonist [90,91]. Recent transcriptome profiling studies uncovered abnormal expression of many histone-related genes (e.g., HIST1H2BD, HIST1H2BC, HIST1H2BH, HIST1H2BG, HIST1H4K, HIST2H2BE) in the blood of SCZ patients [92,93].…”

Section: Aberrant Histone Acetylation In Psychotic Disordersmentioning

confidence: 99%

An Update on the Epigenetics of Psychotic Diseases and Autism

2015

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The examination of potential roles of epigenetic alterations in the pathogenesis of psychotic diseases have become an essential alternative in recent years as genetic studies alone are yet to uncover major gene(s) for psychosis. Here, we describe the current state of knowledge from the gene-specific and genome-wide studies of postmortem brain and blood cells indicating that aberrant DNA methylation, histone modifications and dysregulation of micro-RNAs are linked to the pathogenesis of mental diseases. There is also strong evidence supporting that all classes of psychiatric drugs modulate diverse features of the epigenome. While comprehensive environmental and genetic/epigenetic studies are uncovering the origins, and the key genes/pathways affected in psychotic diseases, characterizing the epigenetic effects of psychiatric drugs may help to design novel therapies in psychiatry.

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Section: Aberrant Histone Acetylation In Psychotic Disordersmentioning

confidence: 99%

An Update on the Epigenetics of Psychotic Diseases and Autism

2015

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“…The first possibility could gain support by the reported histochemical alterations in nuclear chromatin of neutro phils of schizophrenics (Issidorides and Stefanis, 1975;Stefanis and Issidorides, 1976) as well as by the findings of Kucera et al (1971). Based on the previous work of Erban and Hanzlicek (1971) they determined the pycnotic quotient (Qp), i.e., the ratio of the number of white cells with pycnotic nucleus in oxygenated blood to the number of the pycnotic cells in non-oxygenated blood in children of schizo phrenic mothers.…”

Section: Lysozymementioning

confidence: 58%

“…(Ibragimova, 1970) and impaired phagocytic capacity of neutrophils (Przybylska, 1973). Subsequent studies showed chromatin and membrane histochemical alterations in neutro phils of schizophrenics and suggested that genomic expression abnormalities might be re lated to schizophrenic illness (Issidorides andStefanis, 1975: Stefanis andIssidorides, 1976).…”

Section: Introductionmentioning

confidence: 99%

Enzyme Activity of G-6-PD, γ-GT and Lysozyme in White Cells of Schizophrenics

Alevizos¹,

Stefanis²

1980

Neuropsychobiology

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In a controlled study the activity of glucose-6-phosphate dehydrogenase (G-6-PD) in red and white blood cells, γ-glutamyl transpeptidase (γ-GT) and lysozyme in serum and white blood cells was studied in 22 drug-free schizophrenic patients and 17 healthy volunteers. The activities of the above enzymes were found to be reduced in the white cells of schizophrenics compared with controls. The differences in activity of G-6-PD in red cells and of γ-GT and lysozyme in serum between the two groups were not revealed as significant. The observed low enzyme activities might provide a further basis for interpreting the reported functional deficiency in neutrophils of schizophrenics. Possible mechanisms in relation to biological abnormalities in schizophrenia are discussed.

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“…Since differential chromatin condensation seems to be the most likely factor determining stainability with PTAH, Issidorides and colleagues [1] explored the possibility of adapting the PTAH method to electron microscopy [1,21]. The implication is that the compact chromatin prevents, through steric hindrance, the penetration and binding of the large molecular weight anionic PTAH reagent (3400 MW) to the histone's basic groups.…”

mentioning

confidence: 98%

“…Keywords: ammoniacal silver reaction (ASR), chromatin, histones, leukocytes, phosphotungstic acid hematoxylin (PTAH), schizophrenia, ultrastructure Studies on peripheral blood leukocytes of schizophrenic patients have shown in the electron microscope that decondensation of the chromatin constitutes a biological marker, indicating a possible increase in genomic expression [1]. This increase depends on chromatin decondensation by dissociation of lysinerich linker histone (LH) H1 from the nucleosomes.…”

mentioning

confidence: 98%

Chromatin Alterations in Leukocytes of First-episode Schizophrenic Patients

Kloukina-Pantazidou¹,

Havaki²,

Chrysanthou‐Piterou

et al. 2010

Ultrastructural Pathology

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Studies of peripheral blood leukocytes of schizophrenic patients have shown in electron microscopy (EM) that decondensation of the chromatin constitutes a biological marker indicating increased genomic expression. Since this increase depends on chromatin relaxation by dissociation of lysine-rich histone H1 from nucleosomes, with exposure of arginine residues of core histones, the ratio of arginine to lysine residues in each nucleus represents a reliable measure of activation. Lysine- and arginine-rich proteins are demonstrable in light microscopy (LM), differentially, as yellow and black, respectively, with the ammoniacal silver reaction (ASR). Application of ASR on leukocyte pellets before they are dehydrated and embedded in epoxy resins gives reliable results in semithin sections. In thin sections the ASR method localizes only the amino acid arginine by forming deposits of electron-opaque particles, visualized in the EM. Leukocytes of 12 first-episode schizophrenic patients and 5 controls were used. Light micrographs of the semithin sections were inserted in a personal computer. The percentage of lysine and arginine was measured in 300 nuclei per subject. Morphometry showed that lymphocytes of schizophrenic patients have increased ratios of arginine to lysine, compared to controls, indicating activation; neutrophils of the patients have even a higher ratio, indicating an abnormal condition of the genome. Chromatin conformational changes are also evident by phosphotungstic acid hematoxylin (PTAH) block staining, which reveals condensed chromatin as an electron-lucent area in the nuclei, and decondensed chromatin as an electron-dense area. Because decondensed chromatin is a biological marker of schizophrenia, the efficacy of these methods to demonstrate this particular state offers a tool for early diagnosis, since first-episode schizophrenic patients have a better prognosis when treatment is started promptly, at the beginning of the disease.

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Altered chromatin ultrastructure in neutrophils of schizophrenics

Cited by 42 publications

References 14 publications

An Update on the Epigenetics of Psychotic Diseases and Autism

An Update on the Epigenetics of Psychotic Diseases and Autism

Enzyme Activity of G-6-PD, γ-GT and Lysozyme in White Cells of Schizophrenics

Chromatin Alterations in Leukocytes of First-episode Schizophrenic Patients

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