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Autism and dopaminergic system: sexual differences, molecular and behavioral analyzes

Grant number: 17/04642-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Luciano Freitas Felicio
Grantee:Luana Carvalho Cezar
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Autism is a complex developmental disorder characterized by behavior commitment. Prenatal VPA exposure creates symptoms similar to those found in human being. In our previous study, we demonstrated that prenatal VPA exposure causes cognitive inflexibility, commitment to vocalization and socialization, and also decreased striatal TH in male offspring. Those results suggests an autistic-like phenotype related to dopaminergic system functional modifications. Since that the dopaminergic system is a potential trigger to the treatment of autism symptoms, this project is going to verify possible neurobiochemistry, molecular and behavior alterations about the autism commitment in rats exposed to VPA prenatally by administration of postnatal acute or chronic methylphenidate treatment. Methylphenidate selectively increases DA release into cortical and striatal brain domains, becoming a possible revealer and activator of dopaminergic systems. Chronic administration of methylphenidate might provide structural changes in dopamine systems, and translate that neuroplasticity into behavior alterations. To investigate dopaminergic changes it is going to be evaluate the stereotypic behavior and social interaction, protein and gene expression in dopamine receptors and provide the monoamine concentration and its metabolites in striatal and pre-frontal cortex in rats prenatally exposed to VPA and challenged with acute or chronic administration of postnatal methylphenidate. Our study has potential to provide relevant biological and clinical information. (AU)