Effects of neonatal hypoxia on the development of schizophrenia: role of the adenosinergic system

• Grant number: 17/19972-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2018
• End date: January 31, 2020
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Mariana Bendlin Calzavara
• Grantee: Mariana Bendlin Calzavara
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ary Gadelha de Alencar Araripe Neto ; Jair Ribeiro Chagas ; Tatiana Rosado Rosenstock ; Vanessa Costhek Abílio

Abstract

Recently much attention has been focused on the role of neurodevelopment in schizophrenia. It is believed that the most evident clinical manifestation of schizophrenia (positive symptoms), reflecting the striatal hyperdopaminergic state, is the final result of changes that emerge from the interaction between genetic, environmental and neural factors related to life-long development. Pharmacotherapy of schizophrenia based on the dopaminergic hypothesis remains unsatisfactory for the treatment of negative symptoms and cognitive deficits related to this disease. Adenosine is a homeostatic modulator that is capable of affecting different complex networks such as: neurotransmitter-dependent, bioenergetic and epigenetic pathways. In this sense, adenosine seems to be a promising candidate in the correction of the functional imbalance found in schizophrenia, which may influence the dopaminergic and glutamatergic systems. Evidence points to an important participation of adenosine in neural development and indicates 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, few studies attempt to clarify the mechanisms related to the participation of the main hypoxic pathophysiological hypotheses of schizophrenia. Systems submitted to hypoxia have increased adenosine as one of the adaptive responses. Many of these effects are reversed in permanent alterations that have not yet been well established and seem to play an important role in the pathophysiology of numerous diseases, including schizophrenia. Animal and cellular models may be interesting tools for the study of interventions such as perinatal hypoxia and its repercussions In cerebral and behavioral function that mimic the modifications underlying schizophrenia. This project has as main objective to study the effects of neonatal hypoxia on the development of schizophrenia, evaluating the role of the adenosinergic system in the modulations of dopaminergic and glutamatergic systems. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RAMOS, ALINE CAMARGO; HUNGRIA, FILIPE DE MATTOS; CAMERINI, BIANCA AVANSI; SUIAMA, MAYRA AKIMI; CALZAVARA, MARIANA BENDLIN. Potential beneficial effects of caffeine administration in the neonatal period of an animal model of schizophrenia. Behavioural Brain Research, v. 391, AUG 5 2020. (15/26820-0, 17/19972-3, 14/06961-5)