Razi Journal of Medical Sciences

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 positively or negatively gene expression. Hypothyroidism during pregnancy and the early period has severe consequences for the developing offspring rat brain. The present investigation examined the effects of graded levels of hypothyroidism, from subclinical to severe, on global gene expression in the developing rat brain. 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 (PN)20. Maternal blood collected for thyroid hormone analysis.  RT-PCR was used to compare BDNF, NT3, NGF ,Bcl2 gene expressions in the brain of postnatal day (PN) 20 pups experiencing graded degrees of thyroid hormone insufficiency induced by delivery of 0, 50, 75 and 100 ppm MMI to the dam. Daily body weight in dams and pups, the number of pups at birth, eye-closure opening day and BDNF expression in brain extract was determined in the preweaning rats as a function of MMI exposure. This data indicate that genes driving important developmental processes in developing rodent CNS are sensitive to relatively modest perturbations of the thyroid axis and that the level of gene expression is related to the degree of hormone reduction. Altered patterns of gene expression in developing rat brain indicate that thyroid disease induces structural and functional abnormalities in the developing central nervous system

Keywords: Methimazole, genomics, cortex, hippocampus, subclinical hypothyroidism

     

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