Effect of Maternal Hypothyroidism on BDNF Expression in Developing Rat Brain

Thyroid hormone is essential for proper development of brain and modest degrees of developmental thyroid hormone insufficiency can result severe neurological deficits. We used an animal model to study the role of thyroid hormones (THs) during the gestation days and early postnatal days on developing rat brain. Dose-dependent thyroid hormone insufficiency in dams was induced by methimazole (MMI). In the first study-group thyroid hormone deficiency was induced by delivery of methimazole (MMI) to dams via drinking water at the doses of 50, 75 and 100 ppm from early gestation (GD 3) until weaning of the pups (PN20). In the second study-group hypothyroid rats were treated with 200 mu g of thyroxine hormone. Pups were sacrificed on postnatal days (PN) 20. Maternal blood collected for thyroid hormone analysis. Cerebellum, medulla, hippocampus, cortex, olfactory bulbs were separated from dissected brain and relative expression of BDNF gene transcripts known to play critical roles in developing rat brain, were determined by RT-PCR. Daily body weight in dams and pups, the number of pups at birth, the eye-closure opening day and BDNF expression in brain extract was determined in the preweaning rats as a function of MMI exposure. The results indicate that genes driving important developmental processes during early brain development are sensitive to perturbations of the thyroid axis function.