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Vocalization behavior and genetic investigation in mouse pups born under an experimental condition of subclinical maternal hypothyroidism: a link for Autism Spectrum Disorder?

Grant number: 17/08377-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2017
Effective date (End): May 31, 2019
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Carlos Alberto Avellaneda Penatti
Grantee:Deborah Monteiro dos Santos
Home Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil

Abstract

Autism is a neurodevelopmental disorder whose main clinical manifestation lies on altered social behavior with predominant deficit of alo- and self-communication causing impact in both individual aspect of living as in the social aspect of life in community. Such changes relate to complex ontogenetic disturbances, which involve neuronal cell-signaling molecules and time-specific development genes that create a coordinated cascade of events during embryonic development of cortical neural networks in fetal and neonatal periods. Knowing the importance of clinical manifestation and epidemiology of cognitive disorders, the present study aims to characterize the insufficient communication of male and female newborn and infant pups born from pharmacological subclinical or mild maternal hypothyroidism condition using a C57BL/6 mouse animal model. When compared with controls, the experimental group of pups will be born from dams orally given 0.05% methimazole one month just prior to mating (with normal thyroid function males) and pregnancy. In this model, the thyroid function recovery happens during the early first days of pregnancy after the methimazole-induced hypothyroidism, a critical time for embryonic neurodevelopment. This first generation offspring will be evaluated by the behavioral tests of vocalization and place preference and will be correlated with RT-PCR analysis of expression of the SHANK3, Foxp2, CADM1 genes, known markers for disorders in language expression and autism. We will also perform the same behavioral and molecular experiments in a second offspring generation from the same dams without any further exposure to methimazole as negative control. Thus, we expect to determine and quantify altered communication ability in pups born from subclinical or mild hypothyroid environment during early stage in pregnancy, and if there is any dependence of sex or gene expression correlation with communication deficits and autism spectrum disorder. (AU)