[Microglia-neuron interactions in the caudate nucleus in different course of schizophrenia]. / Vzaimodeistviya mikroglii i neironov v khvostatom yadre pri raznykh tipakh techeniya shizofrenii.

OBJECTIVE: To study the ultrastructure of microglia and neurons in contact with each other in the head of the caudate nucleus in continuous schizophrenia (CS) and paroxysmal-progressive schizophrenia (PPS) as compared to controls and to analyze correlations between the parameters of microglia and neurons in the control and schizophrenia groups. MATERIAL AND METHODS: Post-mortem electron microscopic morphometric study of microglia and neurons in contact with each other was performed in the head of the caudate nucleus in 9 cases of CS, 10 cases of PPS and 20 controls without mental pathology. Group comparisons were made using analysis of covariance and Pearson correlation analysis. RESULTS: The PPS group showed increased numerical density of microglia in young (≤50 years old) patients compared to elderly (>50 years old) controls and increased area of endoplasmic reticulum vacuoles in microglia in young patients compared to young controls. Decreased numerical density of microglia was found in the CS group compared to the PPS group (p<0.05), and increased volume fraction (Vv) and the number of lipofuscin granules in microglia were found in the CS group in elderly patients compared with young and elderly controls. In this group, negative correlations were revealed between the numerical density of microglia, microglia nuclear area and the duration of disease (r= -0.72, p=0.03; r= -0.8; p=0.01). Decreased Vv and the number of mitochondria in microglia and increased area and perimeter of neurons were revealed in both groups compared to the control group. In neurons, increased vacuole area was found in the PPS group and mitochondrial area in the NTS group compared to the control group. Correlation violations were found between the parameters of mitochondria in microglia and neurons in both PPS and CS groups and between the area of mitochondria in neurons and the area of vacuoles in microglia in the CS group compared to the control group. CONCLUSION: Disturbed interactions between microglia and neurons in the caudate nucleus are associated with the types of course of schizophrenia and with microglial reactivity. They might be caused by the damage of energy metabolism in microglia in both types of schizophrenia course and by stress of endoplasmic reticulum in microglia in CS.

Deficit of satellite oligodendrocytes of neurons in the rostral part of the head of the caudate nucleus in schizophrenia.

Increasing evidence implicates compromised myelin integrity and oligodendrocyte abnormalities in the dysfunction of neuronal networks in schizophrenia. We previously reported a deficiency of myelinating oligodendrocytes (OL), oligodendrocyte progenitors (OP) and satellite oligodendrocytes of neurons (Sat-OL) in the prefrontal cortex and the inferior parietal cortex - cortical hubs of the frontoparietal cognitive network and default mode network (DMN) altered in schizophrenia. Deficiency of OL and OP was also detected in the head of the caudate nucleus (HCN), which accumulates cortical projections from the associative cortex and is the central node of these networks. However, the number of Sat-Ol per neuron in schizophrenia has not been studied in the HCN. In the current study we estimated the number of Sat-Ol per neuron in the rostral part of the HCN in schizophrenia (n = 18) compared to healthy controls (n = 18) in the same section collection that was previously used to study the number Ol and OP. We found a significant decrease of the number of Sat-Ol per neuron (- 50%, p < 0.001) in schizophrenia as compared to normal controls. Considering that the rostral part of the HCN is an individual network-specific projection zone of the DMN, the deficit of Sat-Ol found in schizophrenia may be related to the dysfunctional DMN-HCN connections, which has been repeatedly described in schizophrenia. The dramatic decrease of the number of Sat-Ol per neuron may be partially related to a pronounced excess of dopamine concentration in the rostral part of the HCN in schizophrenia.

Microglia-neuron interactions in prefrontal gray matter in schizophrenia: a postmortem ultrastructural morphometric study.

This study addressed the question of whether the interaction between neurons and satellite microglia (SatMg) is abnormal in schizophrenia. SatMg-neuron communication at direct contacts between neuronal soma is essential for neuroplasticity as SatMg can regulate neuronal activity. A postmortem ultrastructural morphometric study was performed to investigate SatMg and adjacent neurons in layer 5 of the prefrontal cortex in 21 cases of schizophrenia and 20 healthy controls. Density of SatMg was significantly higher in the young schizophrenia group and in the group with illness duration ≤ 26 years as compared to controls. We found lower volume fraction (Vv) and the number (N) of mitochondria and higher Vv and N of lipofuscin granules and vacuoles in endoplasmic reticulum in SatMg in the schizophrenia compared to the control brain. These changes progressed with age and illness duration. A significantly higher soma area and Vv of vacuoles of endoplasmic reticulum were revealed in neurons in schizophrenia as compared to controls. Negative significant correlations between N of vacuoles in neurons and N of mitochondria in SatMg were found in the control group but not in the schizophrenia group. Area of vacuole in neurons was significantly positively correlated with Vv and area of mitochondria in SatMg in the control group and negatively in the schizophrenia group. Correlation coefficients between these parameters differed significantly between the groups. These results indicate disturbed SatMg-neuron interactions in the schizophrenia brain and suggest a key role of mitochondrial abnormalities in SatMg in these disturbances.

[Reduced numerical density of oligodendrocytes and oligodendrocyte clusters in the head of the caudate nucleus in schizophrenia]. / Snizhenie chislennoi plotnosti oligodendrotsitov i klasterov oligodendrotsitov v golovke khvostatogo yadra pri shizofrenii.

OBJECTIVE: Morphometric estimation of the numerical density of oligodendrocytes (NcOl) and numerical density of oligodendrocyte clusters (NvOlC) in the rostral part of the caudate head nucleus associated with the cortical regions of the default network in the norm and in schizophrenia. MATERIAL AND METHODS: NcOl and NvOlC were determined in the gray matter of the rostral part of the head of the caudate nucleus in Nissl-stained sections using optical dissector in postmortem brains in 18 schizophrenia and 18 healthy control cases. RESULTS: The NvOl (-20%, p<0.001) and NvOlC (-28%, p<0.001) were decreased in the schizophrenia group as compared to the control groups. The NvOl correlated with the NvOlC (R≥0.88, p<0.001) in both groups while a lack of correlations was previously found in the central part of the caudate head. CONCLUSION: The detected deficits of the NcOl and NvOlC is an agreement with prominent suppressing of cortico-striatal connections and reduced density of gray matter in this part of the caudate in schizophrenia. The differences in the pattern of correlations as compared to the central part of this structure might be associated with the specific features of functional activity of default-mode and fronto-parietal networks associated with these parts of caudate nucleus.

[Specific interactions between microglia and oligodendrocytes in white matter in continuous schizophrenia]. / Osobennosti vzaimodeistviya mikroglii i oligodendrotsitov v belom veshchestve pri nepreryvnotekushchei shizofrenii.

OBJECTIVE: To study the ultrastructure of microglia adjacent to oligodendrocytes in white matter of the prefrontal cortex in continuous schizophrenia (CSch) as compared to controls and attack-like schizophrenia (ASch) and to perform correlation analysis between the parameters of microglia and adjacent oligodendrocytes previously detected in both clinical types of schizophrenia. MATERIAL AND METHODS: Electron microscopic morphometric study of microglia adjacent to oligodendrocytes was performed in postmortem white matter of the prefrontal cortex (BA10) in 9 cases of CSch, 8 cases of ASch and 20 healthy controls. Group comparisons were made by ANCOVA and Pearson correlation analyses. RESULTS: The reduction of volume fraction (Vv) and the number of mitochondria in microglia was found in elderly subjects (>50 y.o.) as compared to young controls (60%, p<0.05), and the increase in these parameters of lipofuscin granules were detected in elderly subjects as compared to elderly controls in CSch (470%, 606%, p<0.001). Vv and the number of mitochondria in microglia correlated negatively with area of heterochromatin in microglia (r≥-0.7, p<0.05), and area of lipofuscin correlated positively with area of heterochromatin in microglia (r=0.76, p<0.05) and with illness duration (r=0.7, p<0.05) only in the CSch group. The numerical density of microglia was not changed in both schizophrenia groups. Area of heterochromatin was increased in both groups as compared to controls (p<0.05) and correlated negatively with the numerical density of microglia in the CSch group. The number of mitochondria in oligodendrocytes (reduced in CSch) correlated positively with the number of mitochondria in microglia and negatively with Vv of lipofuscin granules in microglia and with area of microglial nucleus only in the CSch group. CONCLUSION: Specific features of CSch as compared to ASch might be associated with the disturbances of mitochondrial and lipid metabolism in microglia, dysfunction of nucleus and accelerated aging of microglia that might lead to alterations of mitochondrial metabolism in oligodendrocytes.

Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia.

Microglial activation has been proposed to contribute to the pathogenesis of schizophrenia. The present study addressed the questions of whether microglial reactivity is involved in the course of schizophrenia and is associated with aging. Transmission electron microscopy and morphometry were applied to estimate microglial density and ultrastructural parameters in layer 5 of the prefrontal cortex (BA10) in postmortem 21 chronic schizophrenia and 20 healthy control cases. A significant increase in microglial density was found in the schizophrenia group (+20 %), in young group (≤50 y.o.), in shorter duration of disease (≤26 yrs.) group, in early age at onset of disease (≤ 21 y.o.) group as compared to controls (p < 0.05) and in young schizophrenia group as compared to both young and elderly (>50 y.o.) controls (p < 0.05). Volume fraction (Vv) of mitochondria was significantly lower and area of lipofuscin granules was significantly higher in young and elderly schizophrenia groups as compared to young and elderly controls. Vv of lipofuscin granules strongly positively correlated with age and duration of disease in the schizophrenia group. Vv and the number (N) of lipofuscin granules were higher in longer duration (>26 yrs.) group as compared to shorter duration group (p < 0.01). Vv and N of vacuoles were increased in longer duration group as compared to controls (p < 0.01). The study provides evidence for microgliosis associated with age, duration of disease and age at onset of disease, progressive dystrophy and accelerated aging of microglia in gray matter of the prefrontal cortex in schizophrenia.

[Microglial reactivity in the prefrontal cortex in different types of schizophrenia]. / Reaktivnost' mikroglii v prefrontal'noi kore pri raznykh tipakh techeniya shizofrenii.

OBJECTIVE: To estimate microglial density and the ultrastructural parameters of microglia in the prefrontal cortex in chronic attack-like and continuous schizophrenia as compared to healthy controls. MATERIAL AND METHODS: Postmortem electron microscopic morphometric study of microglia was performed in the prefrontal cortex (layer 5, Brodmann' area 10). Ten cases of attack-like schizophrenia, 9 cases of continuous schizophrenia and 20 controls were studied. Microglial density, areas of cell and nucleus, nucleus/cytoplasm ratio, volume fraction and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. ANCOVA was used for statistical analysis. RESULTS: A significant decrease in volume fraction and the number of mitochondria and increase in these parameters of lipofuscin granules were found in both groups as compared to the control group. The group of attack-like schizophrenia showed a significant increase in area of vacuoles as compared to the control group, a significant increase in microglial density as compared to controls and in the young (≤50 yrs.old) subgroup as compared to the elderly (>50 yrs.old) control subgroup. In this group, areas of cell and nucleus were significantly higher in the young subgroup as compared to elderly controls, the elderly subgroup of attack-like schizophrenia and the young subgroup of continuous schizophrenia. An increase in the areas of microglia and the nucleus of microglia in young patients was found in comparison with the elderly from the control group, elderly patients with attack-like schizophrenia and young patients with continuous schizophrenia. Significant negative correlations of areas of cell and nucleus and the number of mitochondria with age and positive correlations of area of lipofuscin granules with age and illness duration were found in attack-like schizophrenia in contrast to continuous schizophrenia. CONCLUSION: Chronic attack-like schizophrenia is associated with increased reactivity in young age and dystrophic changes of microglia progressive with age and illness duration. Continuous schizophrenia is associated with reduced microglial reactivity, dystrophic and non-progressive changes of microglia.

Reduced density of oligodendrocytes and oligodendrocyte clusters in the caudate nucleus in major psychiatric illnesses.

Functional dysconnectivity in schizophrenia and affective disorders may be associated with myelin and oligodendrocyte abnormalities. Altered network integration involving the caudate nucleus (CN) and metabolic abnormalities in fronto-striatal-thalamic white matter tracts have been reported in schizophrenia and impaired patterns of cortico-caudate functional connectivity have been found in both bipolar disorder (BPD) and schizophrenia compared to healthy controls. Postmortem studies have found ultrastructural dystrophy and degeneration of oligodendrocytes and dysmyelination in the CN in schizophrenia and BPD. We aimed to test the hypothesis that oligodendrocyte density may be reduced in the CN in major psychiatric disorders and may thereby form the cellular basis for the functional dysconnectivity observed in these disorders. Optical disector was used to estimate the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters (OLC) in the CN of cases with schizophrenia, BPD and major depressive disorder (MDD) and in normal controls (15 cases per group). A significant reduction in the Nv of oligodendrocytes was found in schizophrenia and BPD as compared to the control group (p < 0.05), and the Nv of OLC was significantly lowered in schizophrenia and BPD compared to controls (p < 0.05). There were no significant differences between MDD and control groups. The Nv of OLC was significantly decreased in the left hemisphere in schizophrenia as compared to the left hemisphere of the control group (-52%, p < 0.01). The data indicates that a decreased density of oligodendrocytes and OLC could contribute to the altered functional connectivity of the CN in subjects with severe mental illnesses.

[Abnormalities of oligodendrocyte clusters in supra- and infragranular layers of the prefrontal cortex in schizophrenia]. / Narusheniia klasterizatsii oligodendrotsitov v supra- i infragranuliarnykh sloiakh polia 10 prefrontal'noi kory pri shizofrenii.

AIM: A deficit of cortical gray matter myelination in the frontal lobes has been reported in schizophrenia in neuroimaging studies. Previously the decrease in the numerical density (Nv) of oligodendrocytes (NvOl) in layers 3 and 5 in area 10 of the prefrontal cortex (PFC) has been reported in schizophrenia. Oligodendrocyte progenitors proliferate in the adult human brain and form oligodendrocyte clusters for functional-dependent adaptive myelination. We aimed to estimate the NvOl and Nv of oligodendrocyte clusters (NvOlC) in supra- and infragranular sublayers of the PFC in schizophrenia and healthy controls. MATERIAL AND METHODS: 17 chronic schizophrenia subjects and 20 healthy matched controls were studied in Nissl-stained sections in sublayers 3a- 3c and 5a of the PFC by stereological optical dissector method. RESULTS AND CONCLUSION: The NvOl and the NvOlC were significantly decreased in supra- (32%, p<0.02) and infragranular sublayers (50%, p<0.001) of the PFC in the schizophrenia group as compared to controls. The Nv OlC/Nv Ol ratio decreased significantly in the schizophrenia group only in sublayers 3a (p=0.015) and 5a (p<0.001). In the control group, the NvOlC was positively correlated with the NvOl in sublayers 3b, 3c and 5a (R≥0.59; p≤0.006). In the schizophrenia group, a significant correlation between the parameters was found only in sublayer 5a (R=0.8; p<0.001). The deficit of oligodendrocyte clusters might be associated with altered proliferation and/or maturation of oligodendrocyte progenitors in schizophrenia. Specific alterations of the Nv OlC/Nv Ol ratio might be due to different connectivity of supra- and infragranular sublayers of the PFC and their disturbances in schizophrenia.

[Ultrastructural pathology of oligodendrocytes in white matter in continuous attack-like schizophrenia and a role for microglia]. / Ul'trastrukturnaia patologiia oligodendrotsitov v belom veshchestve pri pristupoobrazno-progredientnoi shizofrenii i rol' mikroglii.

AIM: Previously the authors have reported the ultrastructural pathology and deficits of oligodendrocytes in gray and white matter of the prefrontal cortex in continuous paranoid schizophrenia. The aim of the present work was to study the effects of microglia on the ultrastructure of oligodendrocytes in white matter underlying the prefrontal cortex (BA10) in attack-like schizophrenia. MATERIAL AND METHODS: Postmortem morphometric electron microscopic study of oligodendrocytes in close apposition to microglia was performed in white matter underlying the prefrontal cortex (BA10). Nine cases of chronic attack-like schizophrenia and 20 normal controls were studied. Areas of oligodendrocytes, volume density (Vv) and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. Group comparison was performed using ANCOVA. RESULTS: The schizophrenia group differed from the control group by paucity of ribosomes in cytoplasm of oligodendrocytes, cytoplasm swelling, a significant increase in Vv and number of vacuoles and lipofuscin granules. Significant correlations between the parameters of vacuoles and lipofuscin granules and mitochondria were found only in the schizophrenia group. CONCLUSION: Dystrophic alterations of oligodendrocytes apposed microglial cells were found in the white matter of the prefrontal cortex in chronic schizophrenia as compared to controls. Microglia might contribute to abnormalities of lipid and protein metabolism of oligodendrocytes.

[Deficit of oligodendrocytes in the frontal cortex in schizophrenia]. / Defitsit oligodendrotsitov v lobnoi kore pri shizofrenii.

AIM: Oligodendrocyte abnormalities are thought to be one of the key cellular pathologies involved in disturbances of neuronal connectivity in schizophrenia. MATERIAL AND METHODS: The density of oligodendrocytes in layer III of the prefrontal cortex, BA10, in schizophrenia (n=20) was compared to controls (n=20) using optical dissector method. MANCOVA was applied for group comparisons. RESULTS AND CONCLUSION: The density of oligodendrocytes was significantly lower in each sublayers of layer III (≤20% p≤0.05) in the schizophrenia group as compared to the control group. The deficit of oligodendrocytes in the prefrontal cortex in schizophrenia may be of developmental origin or the result of alterations in the neural tissue of the brain during disease course.

[Ultrastructural pathology of oligodendrocytes in the white matter in continuous paranoid schizophrenia: a role for microglia]. / Ul'trastrukturnaia patologiia oligodendrotsitov v belom veshchestve pri nepreryvnotekushchei paranoidnoi shizofrenii: rol' mikroglii.

AIM: Previously the authors have reported the ultrastructural pathology and deficit of oligodendrocytes in gray and white matter of the prefrontal cortex in schizophrenia. The aim of the study was to determine of the effects of microglia on the ultrastructure of oligodendrocytes in the white matter underlying the prefrontal cortex in continuous schizophrenia. MATERIAL AND METHODS: Postmortem morphometric electron microscopic study of oligodendrocytes in close apposition to microglia was performed in white matter underlying the prefrontal cortex (BA10). Eleven cases of chronic continuous schizophrenia and 11 normal controls were studied. Areas of oligodendrocytes, of their nuclei and cytoplasm, volume density (Vv) and the number of mitochondria, vacuoles of endoplasmic reticulum and lipofuscin granules were estimated. Group comparison was performed using ANCOVA. RESULTS: The schizophrenia group differed from the control group by paucity of ribosomes in the cytoplasm of oligodendrocytes, a significant decrease in Vv and the number of mitochondria and increase in the number of lipofuscin granules. Significant correlations between the parameters of lipofuscin granules, mitochondria and vacuoles were found only in the schizophrenia group. The number of lipofuscin granules were correlated positively with the illness duration. CONCLUSION: Dystrophic alterations of oligodendrocytes attached to microglial cells were found in the white matter of the prefrontal cortex in chronic paranoid schizophrenia as compared to controls. The data obtained suggest that microglia might contribute to abnormalities of energy, lipid and protein metabolism of oligodendrocytes in schizophrenia.

[Ultrastructural changes of myelinated fibers in the brain in continuous and attack-like paranoid schizophrenia]. / Ul'trastrukturnye izmeneniya mielinovykh volokon v golovnom mozge pri nepreryvnotekushchei i pristupoobraznoi paranoidnoi shizofrenii.

AIM: Previously the authors have reported the ultrastructural pathology of myelinated fibers (MF) in the brain in schizophrenia. The aim of the present study was to compare the effect of disease course on ultrastructural changes of MF. MATERIAL AND METHODS: Postmortem electron microscopic morphometric study of MF was performed in the prefrontal cortex, caudate nucleus and hippocampus in 19 cases of paranoid schizophrenia. Fourteen cases of continuous schizophrenia, 5 cases of attack-like schizophrenia and 25 normal matched control cases were studied. The proportion (percentage) of pathological MF was estimated in the prefrontal cortex, layer 5, CA3 area of hippocampus, pyramidal layer, and in the head of the caudate nucleus. RESULTS: The percentage of MF having axonal atrophy and swelling of periaxonal oligodendrocyte process was significantly higher in both continuous and attack-like schizophrenia in all brain structures studied as compared to the control group. In the hippocampus and caudate nucleus, this parameter was increased significantly in attack-like schizophrenia as compared to continuous schizophrenia. In the prefrontal cortex. The percentage of the pathological MF having signs of deformation and destruction of myelin sheaths increased significantly only in continuous schizophrenia as compared to the control group. CONCLUSION: MF pathology is similar in attack-like and continuous paranoid schizophrenia but differ by the degree of severity of pathological MF. Abnormalities in MF contribute to the disconnectivity between the prefrontal cortex, caudate nucleus and hippocampus.

[A possible relationship between disturbed interhemispheric asymmetry and a decrease in perineuronal oligodendrocytes in schizophrenia]. / Vozmozhnaya svyaz' narusheniya mezhpolusharnoi asimmetrii pri shizofrenii so snizheniem chisla perineironal'nykh oligodendrotsitov.

AIM: To specify a possible role of oligodendrocyte deficit in the development of interhemispheric asymmetry. MATERIAL AND METHODS: Perineuronal oligodendrocytes were counted in layer III, Broadmann area 39, in Nissl-stained sections in both hemispheres of post-mortem brain samples of patients with schizophrenia and controls (healthy people). RESULTS AND CONCLUSION: The left-hemispheric asymmetry of perineuronal oligodendrocytes was found in the control group. A decrease of this parameter by 22% and the absence of the interhemispheric asymmetry were noted in patients with schizophrenia. It has been concluded that perineuronal oligodendrocyte deficit in the inferior parietal cortex in schizophrenia can contribute significantly to disturbed interhemispheric asymmetry of this brain structure.

Ultrastructural alterations of oligodendrocytes in prefrontal white matter in schizophrenia: A post-mortem morphometric study.

OBJECTIVE: Neuroimaging studies showed abnormalities in frontal white matter (WM) in schizophrenia that were associated with clinical symptoms. Previously, we reported ultrastructural alterations of myelinated fibers and reduction in the numerical density of oligodendrocytes in BA 10 WM in patients with schizophrenia. We aimed to perform a qualitative and morphometric study of the ultrastructure of oligodendrocytes in BA 10 WM in schizophrenia and in normal controls. METHODS: The study was performed using electron microscopy and morphometry. Size, volume density (Vv) and the number (N) of organelles of oligodendrocytes were estimated in 21 patients with schizophrenia and 20 normal controls. The data were examined using the Kolmogorov-Smirnov test for normality. Pearson correlation analysis was performed to assess possible correlations between the parameters measured and age, post-mortem interval, neuroleptic treatment and duration of the disease. Comparisons between the schizophrenia patients and controls were performed using ANCOVA tests. RESULTS: We found oligodendrocyte swelling, vacuolation, paucity of ribosomes and mitochondria and accumulation of lipofuscin granules in schizophrenia as compared to controls. Morphometry detected a significant reduction in Vv and N of mitochondria and the increase in Vv and N of lipofuscin granules and vacuoles in oligodendrocytes in the schizophrenic group as compared to controls. CONCLUSION: Alterations of oligodendrocytes in schizophrenia provide evidence for the disturbance of their energy, lipid and protein metabolism in prefrontal WM. Oligodendrocyte abnormalities might disturb axonal integrity and circuitry and contribute to the pathophysiology of schizophrenia.

[The effects of blood serum from schizophrenia patients under olanzapine monotherapy on the ultrastructure of astrocytes in human fetal brain organotypic culture].

OBJECTIVE: To study effects of blood serum (BS) from schizophrenia patients under olanzapine monotherapy on astrocytes in the human fetal brain organotypic culture. MATERIAL AND METHODS: Authors studied the human fetal brain organotypic culture after the application of BS from 20 normals and 33 patients (ICD-10 schizophrenia, paranoid type, F20.02; F20.22) taken before and after 8 and 28 weeks of olanzapine treatment. A qualitative electron microscopic study of glial cells, neurons and neuropil as well as morphometric study of the ultrastructure of astrocytes were performed. RESULTS: Authors found no effects of BS from the patients with schizophrenia on neurons and synaptic contacts. The qualitative and morphometric studies revealed different effects of BS from the patients on the astrocyte ultrastructure before and after olanzapine treatment. The application of BS from untreated schizophrenia patients induced dystrophic alterations of astrocytes, BS from patients who received olanzapine during 8 weeks did not influence the astrocyte ultrastructure. After 28 weeks of olanzapine treatment,a hypertrophy of astrocytes (an increase (р≤0.05) of the area of cells and the number of mitochondria (p=0,015) and unaltered volume density of mitochondria) was found as compared to normal control cultures. CONCLUSION: BS from patients with schizophrenia before and after olanzapine treatment induced opposite types of ultrastructural changes of astrocytes in the human fetal brain organotypic culture. The differences might be due to the previously reported changes of the level of circulating immune complexes and interleukins in blood serum of schizophrenia patients and due to the effects of olanzapine on these parameters.

[Ultrastructural changes of lymphocytes in patients with schizophrenia treated with olanzapine]. / Ul'trastrukturnye izmeneniya limfotsitov u bol'nykh shizofreniei pri lechenii olanzapinom.

OBJECTIVE: to study the effect of olanzapine on the ultrastructure of different populations of lymphocytes and lymphoblasts in patients with schizophrenia. MATERIAL AND METHODS: Authors performed a morphometric study using electron microscopy of lymphocytes in 56 patients with schizophrenia treated for 8 weeks with olanzapine and 49 patients treated for 28 weeks with olanzapine before and after treatment. Authors estimated the frequency and ultrastructural parameters of small, large, large activated lymphocytes and lymphoblasts. RESULTS: The frequency of small lymphocytes in patients treated with olanzapine increased and that of large lymphocytes decreased in treated patients as compared to the patients before treatment. The volume fraction of lysosomes increased significantly in small, large and large activated lymphocytes after treatment as compared to the patients before treatment. CONCLUSION: The increased lysosome content in different lymphocyte subpopulations might contribute to the mechanism of olanzapine efficacy.

[Genomic instability in the brain: chromosomal mosaicism in schizophrenia]. / Genomnaya nestabil'nost' v kletkakh golovnogo mozga: khromosomnyi mozaitsizm pri shizofrenii.

AIM: Experimental verification of the hypothesis about the possible involvement of the mosaic genome variations (mosaic aneuploidy) in the pathogenesis of a number of mental illnesses, including schizophrenia and autism: a genetic study of the level of mosaic genome variations in cells of the brain autopsy tissues in healthy controls and schizophrenia. MATERIAL AND METHODS: Autopsy brain tissues of 15 unaffected controls and 15 patients with schizophrenia were analyzed by molecular cytogenetic methods to determine the frequency of chromosomal mutations (the mosaic aneuploidy) in neural human cells. The original collection of chromosome-enumeration DNA probes to autosomes 1, 9, 15, 16, 18 and the sex chromosomes X and Y was used for the interphase cytogenetic analysis of chromosomes in the cells of the brain. RESULTS AND CONCLUSION: The frequency of low-level aneuploidy per individual chromosome was 0.54% (median - 0.53%; 95% confidence interval (CI) CI - 0.41-1.13%) in controls and 1.66% (median - 1.55%; 95% CI -1.32-2.12%) in schizophrenia (p=0.000013). Thus, the three-fold increase in aneuploidy frequency in the brain in schizophrenia was detected. It is suggested that mosaic aneuploidy, as a significant biological marker of genomic instability, may lead to genеtic imbalance and abnormal functional activity of neural cells and neural networks in schizophrenia.

[Effects of schizophrenic blood serum on astrocytes in human fetal brain organotypic culture: a morphometric study].

AIM: To detect cytotoxic effects of blood serum (BS) from schizophrenia patients on astrocytes and neurons in the human fetal brain organotypic culture. MATERIAL AND METHODS: Authors studied the human fetal brain organotypic culture after the application of BS from 20 healthy donors and 33 untreated patients with attack-like progressive schizophrenia (ICD-10: schizophrenia, paranoid type, F20.02; F20.22). The numerical density of degenerating cells was estimated by the optical dissector method in Nissl stained sections. A qualitative electron microscopic study of glial cells, neurons and neuropil as well as morphometric study of the ultrastructure of astrocytes were performed. RESULTS: Authors found no significant effect of BS from patients with schizophrenia on the numerical density of degenerating cells as compared to BS from healthy donors. The qualitative study detected ultrastructural alterations in astrocytes and microglial cells but not in neurons. The morphometric study of astrocytes demonstrated a decrease of the area of astrocytes, their nuclei (р<0.001) and cytoplasm (р<0.05), reduced number of mitochondria (р<0.05) and increase in the number and volume fraction of lypofuscin inclusions (р<0.01). CONCLUSION: The application of BS from untreated schizophrenia patients does not influence the cell survival in human fetal brain organotypic culture and the ultrastructure of neurons and neuropil but induces the hypotrophy of astrocytes and increase in the number of lypofuscin inclusions. The data suggest that astrocytes are specific target for the damage effect of BS from schizophrenia patients.

[Current conceptions about astrocyte reactivity in schizophrenia].

Literature data of the last two decades are summarized. Based on the classic conceptions about structure and functions of astrocytes, the authors review further development of research concerning the role of astroglia in schizophrenia in the following aspects: astrocyte reactivity, ultrastructural astrocyte pathology, markers of gliosis and astrocyte activation in schizophrenia, effect of neuroleptics on astrocytes. In conclusion, the authors emphasize that current studies confirm the absence of astrogliosis in the brain of schizophrenic patients. At the same time, there is evidence of the active involvement of these cells in the pathological process. It is suggested that the astrocyte activation is associated with immune changes in schizophrenia.