Severe Gestational Hypothyroidism Increases BBB Nutrient Transport in the Offspring

Abstract

Brain growth spurt and development is highly influenced by thyroid hormones. We reported earlier that chronic maternal potassium thiocyanate feeding (induced moderate hypothyroidism) resulted in reversible decrease in Blood-Brain Barrier (BBB) glucose transport in the offspring. To assess whether severe hypothyroidism as often seen in endemic areas would have greater effect, we have now determined the thyroid status and BBB nutrient transport in the pups born to dams made severely hypothyroid by feeding 6-n-propyl thiouracil (PTU), the potent antithyroid compound. The pups of PTU fed dams had lower birth weights (P < 0.001) than controls. Their weanling body weight and brain weight were also significantly lower. They were very severely hypothyroid (serum T4 < 0.7 μg/d1 and T3 < 0.5 ng/ml) and surprisingly there was a significant increase in the BBB transport of all three nutrients tested (leucine, tyrosine and 2-deoxy-D-glucose). The increased BBB nutrient transport however does not appear to be due to opening/breakdown of BBB as evident from the lack of extravasation of Evans blue injected into the carotid artery. Interestingly, T3 supplementation to the dams and offspring, could mitigate the changes not only in BBB nutrient transport but also their body and brain weights at weanling.