Structural and biochemical characteristics of synaptic plasticity alterations in psychiatric disorders

Synaptic organization of the brain occurs during pre- and perinatal neurodevelopment, but remodeling of pre-formed contacts continues throughout the life. The aim of this project is to analyze the molecular and structural characteristics of neural networks in schizophrenia (SCH), depression and chemically induced brain trauma. Investigations will be done on the human samples (post mortem brains and plasma from patients suffering from SCH and major depression), animal models (SCH and chemical trauma) and primary cell cultures. Investigation will include determination of proteins involved in regulations of neural and glial development and synaptic plasticity. Neurothrophic factor neuregulin 1 (NLG1), its receptor Erb B4, its downstream protein kinase Akt signaling, as well as the expression of neuroligins and neurexins, and neural cell adhesion molecules (NCAMs) involved in the synapses formation will be studied. Immunohistochemical investigations will be focused on different subpopulations of cortical interneurons, since dysfunctional cortical inhibition has been suggested in SCH. Important part of our research will include assessment of adult neurogenesis by determination of number of cells in proliferation (ki67+ cells) in hillus of dentate gyrus. Revealing the changes in brain synaptic functioning is of extreme importance in understanding the basis of SCH and other psychiatric diseases, and finding of new therapeutic agents.