The effects of thyroid hormone on brain development and function are largely mediated by binding of T3 to its nuclear receptors (TR) to regulate gene expression. Hypothyroidism during the early period of pregnancy has severe consequences for the developing rat brain. The present study examined effects of maternal hypothyroidism (from subclinical to severe) on gene expression in the developing rat brain. Dose-dependent thyroid hormone insufficiency was induced by delivery of methimazole (MMI) to pregnant rats via drinking water from gestation days 3 (GD 3) until sacrifice of pups at PN20.Maternal blood collected for thyroid hormone analysis. QRT-PCR was used to compare Vimentin, Nestin, GFAP, Mag gene expressions in the brain at postnatal day (PN) 20. Pups experiencing thyroid hormone insufficiency induced by delivery of 0, 50, 75 and 100 ppm MMI to the dam. The number of pups at birth, eye closure opening day, daily body weight in dams and pups are measured. BDNF expression were measured by ELISA in brain extract as a function of MMI exposure. The obtained data support the hypothesis that genes driving important developmental processes in developing rodent CNS are sensitive to perturbations of the thyroid axis, and altered pattern of gene expression in developing rat brain indicate that thyroid disease induce structural and functional abnormalities in the developing central nervous system.

Key words: Methimazole, subclinical hypothyroidism, HPT axis, CNS development, gene expression