EMBRIOGENESIS OF NEURONAL ELENENTS (GLIOBLASTS AND GABAA RECEPTORS) IN THE HUMAN BRAIN NEUROIMMUNE SYSTEM UNDER PRENATAL ALCOHOL EXPOSURE

Exposure to alcohol causes imbalances in neuroimmune function and impaired brain development. Alcohol activates the innate immune signaling pathways in the brain. Neuroimmune molecules expressed and secreted by glial cells of the brain (microglia, oligodendroglia) alter the function of neurons and further stimulate the development of alcoholic behavior. Various signaling pathways and brain cells are involved in the transmission of neuroimmune signals. Glial cells are the main sources of immune mediators in the brain, which respond to and release immune signals in the central nervous system. The aim of this study was to study neuronal elements: morphometric parameters of glioblasts, synaptic structures and properties of synaptosomal GABAA-benzodiazepine receptors of the neuroimmune system in the embryogenesis of the human brain under perinatal exposure to alcohol. Changes in glioblasts in the brain tissue of human embryos and fetuses were revealed under conditions of chronic prenatal alcoholization with an increase in gestational age compared with control subgroups: a significant increase in the average number of glioblasts, the length of the perimeters of presynaptic terminal structures, postsynaptic density, presynaptic terminal regions were significantly less (p < 0.01) in the study group than in the control comparison group. Exposure to ethanol leads to a decrease in the affinity of GABAA-benzodiazepine receptors, which affects neuronal plasticity associated with the development and differentiation of progenitor cells (glioblasts and neuroblasts) during embryogenesis of the human brain and leads to suppression of GABAergic function in the brain. This causes a disruption in the interconnection of embryonic cells in the brain, leads to excessive apoptosis due to the activation of glial cells of the nervous tissue, disruption of neuroimmune function in the developing brain, changes in neuronal circuits, as well as a change in the balance of excitatory and inhibitory effects, which affects the functional activity in the central nervous system. Glial activation is a compensatory reaction caused by neuroplastic changes aimed at adapting the developing brain of the embryo and fetus under conditions of neurotoxicity and hypoxia under the influence of prenatal alcoholization of the maternal organism and the effect of ethanol on the fetus. The dynamics of changes in glial elements and receptor activity in the nervous tissue of human embryos and fetuses under conditions of prenatal exposure to alcohol indicates a more pronounced effect of alcohol on the earliest stages of human embryo development, which is of great practical importance in planning pregnancy and the inadmissibility of alcoholization of the mother in order to avoid negative consequences in offspring

Innate and acquired immunity indices in assessing the clinical severity of patients with childhood schizophrenia

The results of previous studies suggest pathogenetic role of immune system in the development of schizophrenia. Examination of adolescent and young adult schizophrenic patients showed that the activity/ level of distinct parameters of innate and acquired immunity correlates with acuity and severity of pathological process in the brain. Presumably, evaluation of immune system characteristics in patients with childhood schizophrenia, concerning severity of their clinical symptoms, along with potential therapeutic aspect, may be the basis for early diagnosis of these conditions, and monitoring and prognosis of the further progression of the disease. The objective of our study was to compare clinical and immunological indices in children with schizophrenia to analyze the possibility of using these parameters for determination of the degree of activity of the pathological process. Sixty-two patients (39 boys and 23 girls) from 4 to 17 years of age with childhood schizophrenia were examined. Psychopathological and psychometric methods (PANSS and CGI-S scales) were used to assess mental state of the patients. Immunological parameters were determined in blood serum taken by fingerprick. Activity of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI) was determined by spectrophotometric method. To determine the level of autoantibodies to S-100B and MBP, we used enzyme immunoassay. The study revealed activation of innate (by activity of LE and a1-PI) and acquired (by the level of autoantibodies to S-100B and MBP neuroantigens) immunity markers in blood serum of children with schizophrenia. Correlation analysis showed the significant positive correlation between complex evaluation of activation level of the immune system and severity of the patients’ state on the CGI-S scale (r = 0.64, p < 0.0001), as well as severity of negative symptoms according to the PANSS scale (r = 0.34, p = 0.0077). The revealed correlations suggest an opportunity for using immunological parameters (LE and a1-PI activity, and antibodies to neuroantigens), as the additional laboratory criteria for the assessment of clinical state in patients with childhood schizophrenia