[An analysis of the relationship between genetic factors and the risk of schizophrenia]. / Analiz svyazi geneticheskikh faktorov s riskom razvitiya shizofrenii.

The etiology and pathogenesis of schizophrenia remain poorly understood, but it has been established that the contribution of heredity to the development of the disease is about 80-85%. Over the past decade, significant progress has been made in the search for specific genetic variants associated with the development of schizophrenia. The review discusses the results of modern large-scale studies aimed at searching for genetic associations with schizophrenia: genome-wide association studies (GWAS) and the search for rare variants (mutations or copy number variations, CNV), including the use of whole exome sequencing. We synthesize data on currently known genes that are significantly associated with schizophrenia and discuss their biological functions in order to identify the main molecular pathways involved in the pathophysiology of schizophrenia.

Urokinase receptor deficiency results in EGFR-mediated failure to transmit signals for cell survival and neurite formation in mouse neuroblastoma cells.

Urokinase-type plasminogen activator uPA and its receptor (uPAR) are the central players in extracellular matrix proteolysis, which facilitates cancer invasion and metastasis. EGFR is one of the important components of uPAR interactome. uPAR/EGFR interaction controls signaling pathways that regulate cell survival, proliferation and migration. We have previously established that uPA binding to uPAR stimulates neurite elongation in neuroblastoma cells, while blocking uPA/uPAR interaction induces neurite branching and new neurite formation. Here we demonstrate that blocking the uPA binding to uPAR with anti-uPAR antibody decreases the level of pEGFR and its downstream pERK1/2, but does increase phosphorylation of Akt, p38 and c-Src Since long-term uPAR blocking results in a severe DNA damage, accompanied by PARP-1 proteolysis and Neuro2a cell death, we surmise that Akt, p38 and c-Src activation transmits a pro-apoptotic signal, rather than a survival. Serum deprivation resulting in enhanced neuritogenesis is accompanied by an upregulated uPAR mRNA expression, while EGFR mRNA remains unchanged. EGFR activation by EGF stimulates neurite growth only in uPAR-overexpressing cells but not in control or uPAR-deficient cells. In addition, AG1478-mediated inhibition of EGFR activity impedes neurite growth in control and uPAR-deficient cells, but not in uPAR-overexpressing cells. Altogether these data implicate uPAR as an important regulator of EGFR and ERK1/2 signaling, representing a novel mechanism which implicates urokinase system in neuroblastoma cell survival and differentiation.

[Immunological parameters in assessing the risk of decompensation in children with mental retardation]. / Immunologicheskie pokazateli v prognozirovanii riska dekompensatsii psikhicheskogo sostoianiia detei s umstvennoi otstalost'iu.

AIM: To analyze the correlation between clinical and immunological parameters in children with mental retardation (MR) in order to explore the possibilities of using immunological data in assessing the severity of patient's condition and predicting a risk of decompensation, exacerbation of mental disorders comorbid to MR. MATERIAL AND METHODS: Seventy-three school children, aged 8-17 years, mean age 12,6±2,4 years, with MR of different genesis and 64 physically and mentally healthy children (control group) of the same age and sex were studied clinically and immunologically. The degree of clinical severity of MR was evaluated by CGI-S scale (the Clinical global impression-severity), the level of intellectual disabilities was evaluated by the Wechsler Intelligence Scale. Enzymatic activity of leukocyte elastase; functional activity of α1-proteinase inhibitor; levels of autoantibodies to neurospecific antigens - S-100b and myelin basic protein were analyzed in the serum of patients and healthy children. RESULTS AND CONCLUSION: The activation of the immune system was associated with comorbid to MR current psychopathological disturbances that were more severe, persistent and required long-term maintenance treatment. Analysis of immunological parameters can be used in children with MR treated in outpatient network as an additional test for the detection of mental state decompensation.

[In vitro effect of psychotropic drugs on the activity of leukocyte elastase].

OBJECTIVE: To investigate the effect of the neuroleptic aminazine (chlorpromazine) and the antidepressant melipramine on the activity of leukocyte elastase (LE). METHODS: The LE activity was measured on a spectrophotometer. Different doses of aminazine and melipramine in terms of therapeutic doses were added to the pooled blood serum sampled from 7 healthy people. RESULTS: Aminazine and melipramine inhibited the LE activity. CONCLUSIONS: The dose-dependent inhibiting effect of aminazine and melipramine was shown.