Stress during neurodevelopment and sociability: possible behavioral and neuronal morphofuncitonal effects

• Grant number: 19/03750-7
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2020
• End date: March 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Eduardo Neves Girardi
• Grantee: Carlos Eduardo Neves Girardi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

This study will employ an animal model of adversity in the neonatal period to characterize neurobiological and behavioral changes due to insults during neurodevelopment. Adverse events during critical phases of neurodevelopment can lead to lasting behavioral and neurobiological consequences, e.g., vulnerability to neuropsychiatric disorders. Among these impairments, morphofunctional changes in the cerebral cortex are highlighted, with important late behavioral consequences, such as sociability, anxiety and cognitive deficits. Maternal care plays an important role in neurodevelopmental homeostasis. Animal models that employ its interruption in the neonatal period have been prominent in research on the late effects of infant adversities. Maternal deprivation for 24 hours (MD) is one of these models and has revealed changes in the dopaminergic transmission system, impairment in sensorimotor processing, increase in anxiety-type behavior and deficit in sociability. Thus, the objective of this work is to analyze short and long-term consequences, triggered by MD, on the dendritic morphology of the cerebral cortex, on different aspects related to social behavior, as well as on dopaminergic neuronal activation underlying the motivation for social stimuli in young age. To that end, the Golgi-Cox technique will be used to evaluate cortical dendritic morphology, behavioral tests to evaluate the motivation to social interaction, and double-staining immunofluorescence to evaluate dopaminergic neuronal activation at core brain structures related to the reinforcing property of social stimuli. Given that impairments in sociability represent an important dysfunctional aspect of neuropsychiatric disorders, these findings may provide insight into the pathophysiology of these disorders, as well as identify possible preventive and therapeutic targets. (AU)