Background: The effects of thyroid hormone on brain development and function are largely mediated by the binding of T3 to its nuclear receptors (TR) to regulate gene expression positively or negatively. Hypothyroidism during the early period of pregnancy and has severe consequences for the developing rat brain.

Aim: To examine effects of maternal hypothyroidism on gene expression in the developing rat brain.

Methods: Dose-dependent thyroid hormone insufficiency was induced by the delivery of methimazole (MMI) to pregnant rats via drinking water from gestation days 3 (GD 3) until the sacrifice of pups at PN20. Results: Maternal blood collected for thyroid hormone analysis. qRT-PCR was used to compare BDNF, NT3, NGF, Bcl2 relative gene expressions in the brain of postnatal day (PN) 20 pups experiencing thyroid hormone insufficiency induced by delivery of 0, 50, 75 and 100 ppm MMI to the dam. Daily body weight in dams and pups and BDNF expression in brain extract were determined in the preweaning rats as a function of MMI exposure. The obtained data indicate that genes driving important developmental processes in developing rodent CNS are sensitive to perturbations of the thyroid axis and the level of gene expression is related to the degree of hormone insufficiently. Altered patterns of gene expression in developing rat brain indicate that thyroid disease induces structural and functional abnormalities in the developing central nervous system. Conclusion: The study suggests a continuum of thyroid disease with neurological disorders. Alteration in BDNF levels in early life could contribute to the adverse neurodevelopmental effects that occur after prenatal hypothyroidism.

Keyword: Methimazole, gene expression, CNS, subclinical hypothyroidism