EVALUATION OF EFFECTS OF NEONATAL HYPOXIA ON SCHIZOPHRENIA DEVELOPMENT: ROLE OF ADENOSINERGIC SYSTEM

Abstract

Recently much attention has been focused on the role of neurodevelopment in schizophrenia. It is believed that the manifestation of schizophrenia, reflecting the striatal hiperdopaminérgico state, is the end result of changes that emerge from the interaction between genetic and environmental factors and related to neural development throughout life. Pharmacotherapy of schizophrenia based on the dopamine hypothesis remains unsatisfactory for the treatment of negative symptoms and cognitive deficits related to this disease. Adenosine is a homeostatic modulator that is able to affect various complex networks as dependent pathways of neurotransmitters, bioenergetics and epigenetics. In this regard, adenosine appears to be a promising candidate in the correction of functional imbalance found in schizophrenia and may influence the dopaminergic and glutamatergic systems. Evidence points to an important adenosine participation in neural development and indicate a potential involvement of this substance in the etiology of schizophrenia. Perinatal hypoxia is one of the most well-established risk factors for the development of schizophrenia, however, there are few studies that attempt to clarify the mechanisms related to the participation of hypoxia in major pathophysiological hypotheses of schizophrenia. Systems subjected to hypoxia is an increase of adenosine as an adaptive responses. Many accrues in permanent changes still not well established effects that seem to play an important role in the pathophysiology of numerous diseases, including schizophrenia. Animal and cell models can be interesting tools for the study of interventions such as perinatal hypoxia and its effects on brain function and behavioral changes that mimic the underlying schizophrenia. This project aims to study the effects of neonatal hypoxia in the development of schizophrenia by assessing the role of adenosinergic system in the modulation of dopaminergic and glutamatergic systems.