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Oligodendrocyte abnormalities are thought to be one of the key cellular pathologies involved in disturbances of neuronal connectivity in schizophrenia.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.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.Цель исследования. Повреждения структуры и нарушение функции олигодендроцитов, возможно, являются одним из ключевых звеньев патогенеза, которые приводят к нарушению межнейрональных связей и дезинтеграции работы нейронных сетей при шизофрении. Материал и методы. Определяли численную плотность олигодендроцитов в слое III поля 10 префронтальной коры при шизофрении (n=20) по сравнению с контролем (n=20) методом оптического диссектора. Статистический анализ MANCOVA применяли для сравнения исследуемых групп. Результаты и заключение. Численная плотность олигодендроцитов достоверно снижена во всех подслоях слоя III (≤20%, p≤0,05) в группе больных шизофренией по сравнению с контролем. Дефицит олигодендроцитов в префронтальной коре при шизофрении может быть результатом нарушения развития нервной системы, а также изменений в ткани головного мозга, происходящих в течение заболевания.

Many hypotheses have been proposed for the pathogenesis of schizophrenia. The most common hypotheses of schizophrenia are dopaminergic, serotoninergic, glutamatergic. There are also assumptions about involvement of other neurochemical systems, in particular GABAergic, in the pathogenesis of schizophrenia. The available data on the damage of GABAergic interneurons, taking into account the results of postmortem, neuroimaging, molecule-genetic, electrophysiological studies in humans and fundamental studies in animals, are discussed. The author suggests that one of the pathophysiological mechanisms of the pathogenesis of schizophrenia may be a disturbance of myelination of GABAergic interneurons leading to a decrease in the number of intra- and interhemispheric coherent connections, and eventually to the development of symptoms of the disease.В научной литературе существует несколько гипотез патогенеза шизофрении. Наиболее распространенные гипотезы шизофрении - дофаминергическая, серотонинергическая, глутаматергическая. Существуют также предположения о вовлеченности в патогенез шизофрении и других нейрохимических систем, в частности ГАМКергической. В представленном обзоре рассматриваются имеющиеся в литературе данные о повреждении ГАМКергических интернейронов при шизофрении с учетом данных постмортальных, нейровизуализационных, молекулярно-генетических, электрофизиологических исследований. Изложена гипотеза патогенеза шизофрении, основу которой составляют нарушения миелинизации ГАМКергических интернейронов, приводящие к уменьшению числа внутри- и межполушарных когерентных связей и возникновению симптомов заболевания.

The aim of the present work was to produce organotypic cultures of human embryo brain tissues, as needed for investigation of the effects of serum factors on mental diseases and their pharmacological treatment. Cultures were made using slices of medulla oblongata from human embryos aged 9-10 weeks, obtained from medical abortions. Free-floating slices were cultured using a modified roller method for four weeks. Light and electron microscopy, along with immunocytochemistry, demonstrated that cultured slices showed differentiation and growth of neurons, astro- and microgliocytes, with formation of the synaptic contacts and glioneuronal interactions typical of organotypic cultures. However, along with differentiated neurons and glial cells, there was some persistence of undifferentiated cellular elements with signs of stem cells and neuron and gliocyte precursor cells. These experiments showed that organotypic roller cultivation of free-floating slices of human embryo brain tissue can be used to study the processes of neuron and gliocyte development, the mechanisms of neurotoxicity and neuroprotection using a variety of morphological (including stereological) and biochemical study methods.

To study the spatial organization of oligodendrocytes and pyramidal neurons in the frontal limbic cortex of patients with schizophrenia and healthy controls, the authors used a method of two-dimensional automated analysis of images. The decrease in the minimal distance between the oligodendrocyte and the nearest neuron by 20% and in the mean and maximal distances between neurons and the nearest oligodendrocytes by 10% and 9%, respectively, was found in the layer III in patients with schizophrenia. Therefore, this method allows to characterize the spatial organization of neurons and glia in the brain cortex not only in the normal brain but also in mental pathology.

To specify a possible role of oligodendrocyte deficit in the development of interhemispheric asymmetry.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).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.Цель исследования. Установление возможной роли дефицита олигодендроцитов в развитии межполушарной асимметрии при шизофрении. Материал и методы. На срезах, окрашенных по методу Ниссля, измеряли число перинейрональных олигодендроцитов в слое III поля 39 (по Бродману) в обоих полушариях аутопсийного мозга при шизофрении по сравнению с контролем (психически здоровые). Результаты и заключение. Установлено наличие левополушарной асимметрии числа перинейрональных олигодендроцитов в контрольной группе. В группе шизофрении выявлено снижение этого показателя на 22% по сравнению с контролем и отсутствие межполушарной асимметрии. Сделан вывод, что дефицит перинейрональных олигодендроцитов в нижней теменной коре при шизофрении может вносить существенный вклад в нарушение функциональной асимметрии этой структуры мозга.

Autopsy samples from the prefrontal cortex were obtained from 22 schizophrenic cases and 22 normal controls. Capillaries and oligodendrocytes were viewed in paraffin sections stained with a Luxol-fast blue + cresyl violet. Electron microscopy was applied to study the ultrastructure of oligodendrocytes. Numerical density of pericapillary oligodendrocytes was measured in layer V of Broadmann's area 10. Subjects with schizophrenia had a significantly lower (-20,8%) numerical density of pericapillary oligodendrocytes compared to controls. The analysis for schizophrenic subgroups with predominantly positive or predominantly negative symptoms revealed a significant decrease in the numerical density of pericapillary oligodendrocytes only in the latter one (-29,4%). The numerical density of pericapillary oligodendrocytes in cases with predominantly positive symptoms also decreased (-8,3%) but not differed significantly from the controls. Electron microscopy revealed the prominent ultrastructural dystrophic and degenerative alterations of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenic brains. The present study points out that the population of pericapillary oligodendrocytes is involved in the pathogenesis of schizophrenia. Damage and loss of pericapillary oligodendrocytes might lead to disruption of the blood-brain barrier and as a result to dysregulation of metabolic trafficking across the blood-brain barrier in the prefrontal cortex in schizophrenia.

Using optical dissector methodology, a morphometric study of numerical density of oligodendroglial cells in layer VI and in adjacent white matter of Broadmann area 10 has been conducted in 23 postmortem brains of schizophrenics and 20 matched controls. Comparing to controls, a significant reduction of numerical density of oligodendroglial cells was found in layer VI (by 31%) and adjacent white matter (by 12%) of schizophrenic patients. The data obtained, as well as ultrastructural signs of oligodendroglial cells apoptosis and necrosis found earlier by the authors, may indicate a loss of these cells in the prefrontal cortex in schizophrenia, which may, in its turn, result in neuronal and high cortical dysfunctions.

Hybridoma technique was used to obtain a clone producing IgG antibodies. Paired helical neurofilaments isolated from the brain of patients suffering from Alzheimer's disease were used as an antigen during preparation of the clone. Antibodies recognize neurons with neurofibrillary changes. Specificity of the obtained antibodies to paired helical filaments was proved immunohistochemically. Monoclonal antibodies obtained are likely to be useful in the determination of the role played by pathological proteins in mutually twisted filaments formation.

A study was made of the effect of autopsy brain extracts from persons with dementias of different origin (Alzheimer's disease and senile dementia) on nervous tissue culture of human fetuses. Light microscopy showed a tendency towards an increase of the astrocyte count and expressivity of their immunocytochemical response to glial fibrillar acid protein after administration of brain extract from persons with Alzheimer's disease. Electron microscopy revealed a substantial rise of the frequency of occurrence of altered microtubules in the processes of ectodermal cells, particularly marked due to the effect of extracts from persons with senile dementia. It was also shown that cytoplasm of hypertrophied astrocytes was loaded with regulated bundles of +glial filaments (primarily in experimental culture series). Brain extracts from persons with Alzheimer's disease induced as well the formation of typical complexes in the synaptic structures.

During autopsy of brains from 17 schizophrenic patients and 14 mentally normal subjects the authors studied metabolic characteristics in hyperchromic neurons, using methods of electron cytochemistry. The parameters of plastic and energy metabolism investigated included ribonucleoproteins (RNP), Mg-activated ATPase and succinate dehydrogenase (SDH). Two types of neurons with a different degree of hyperchromia and a decrease in metabolic activity were identified. The type I neurons were characterized by a marked decrease in the activity of the studied enzymes and the number of RNP particles, type II neurons by almost complete absence of enzymic activity and a sharp decrease in RNP particles. The results obtained make it possible to consider the hyperchromic neuron as a cell with a diminished functional activity.

Biological fluids (blood serum, cerebrospinal fluid) and brain extract obtained from patients with Alzheimer's disease (6 cases), simple senile dementia (5 cases), and other atrophic processes (1 case) were administered into the nutrient media of human fetal brain tissue culture. It was found that brain tissue extract obtained from patients with Alzheimer's disease stimulated accumulation of filamentous material in neurons while the CSF induced the formation of orderly filamentous rings. The effect of blood serum was characterized by nonspecific manifestations in the form of accumulation of structurally heterogeneous lamellar corpuscles.

Electron-cytochemical methods were used to study the distribution of acetylcholinesterase (ACE) activity in the brain in postmortem cases of Alzheimer's disease. The findings showed a decreased number of ACE-positive neural fibers in the upper cortical layers. The reduction was most pronounced in the temporal and parietal lobes of the cortex and absent in the occipital lobe. The disclosed cytochemical changes confirm the presence of disorders in the cholinergic system in the brain cortex in Alzheimer's disease.

Upon cultivation of the brain tissue and skin-muscle tissues of human embryos, a polyimide film was used as a lining. The optimal conditions of the preliminary processing of the lining (sterilization, washing) are described. An easy separation of the polyimide film from the media (in the process of tissue treatment for electron microscope studies) facilitates the use of the material for light and electron microscopy without damaging the culture.

Electron cytochemistry was employed to identify microglial cells by nucleoside diphosphatase (NDPase) in the senile plaques of the autopsy brain in Alzheimer's disease and senile dementia. It has been elucidated that processes of microglial cells enter a senile plaque and are closely connected with amyloid accumulation. A positive reaction to NDPase revealed in the extracellular substance suggests that these cells play an important role in the accumulation of amyloid in a senile plaque.

Monospecific polyclonal antibodies to acid fibrillar astroglial protein allowed to reveal the sites of the filaments accumulation within the cells and perform the characterization of the tissue culture in terms of its cellular composition ectodermal and mesenchymal. The data suggest that in distinct terms of explanation of the human embryonic nervous tissue in the culture identical epitopes (antigen determinants) could be formed by intracellular fibrillar structures even in the cells of different origin.