Characterization and study of peripheral proteins in lymphocytes in schizophrenia

Résumé

The immune hypothesis in schizophrenia is being investigated in depth in recent years, regulatory T lymphocytes are involved in the control of the immune system (SI) and have remained directly linked to changes in certain HLA genes in schizophrenia. The different phases of this disease show changes in number, type of lymphocyte in patients and cellular function. In schizophrenia, an increase in B lymphocytes and a reduction in T lymphocytes have been described, with alterations in the proportions of regulatory T lymphocytes in acute psychosis and during the chronification of the disease. In addition, postmortem studies found lymphocyte infiltration in brain regions of functional relevance for psychosis. In this project we want to study the receptors that are expressed in the lymphocyte membrane of patients with schizophrenia. Identified potential candidates, we will study its functioning, signaling pathways, relationship with other receptors and clinical correlation to identify potential diagnostic biomarkers, therapeutics and predictors of disease evolution. We propose to evaluate the following hypothesis: in the development of the central nervous system the correct functioning of the SI is very important, otherwise it can be the origin of serious mental illnesses. Schizophrenia is a disease of neurodevelopment and its different evolution in patients will make them have a good or bad prognosis. If we get to know the molecular changes that occur in the lymphocytes of the patients, we can deepen the neurobiology of the disease and develop diagnostic and prognostic biomarkers of schizophrenia from peripheral samples. Goals: To study changes in the expression of receptors in lymphocytes of patients with schizophrenia by proteomic analysis with LC-ESI-MS / MS. Investigate changes in cell signaling of receptors using primary cultures and the Jurkat cell line. Relate changes in expression, activation, intracellular translocation with the different stages of disease development (1st psychotic episode, disease stabilization, drug response) Investigate the distribution of receptors in different lymphocyte subpopulations. Correlate changes with clinical evolution. Find a clinical correlation with the severity scales of schizophrenia using PANSS and with anhedonia using SAAS.