phenylthiourea and Disease-Models--Animal

There is a growing body of evidence that subtle decreases in maternal thyroid hormone during gestation can impact fetal brain development. The present study examined the impact of graded levels of thyroid hormone insufficiency on brain development in rodents. Maternal thyroid hormone insufficiency was induced by exposing timed-pregnant dams to propylthiouracil (PTU) at doses of 0, 1, 2, 3, and 10 ppm in the drinking water from gestational d 6 through weaning on postnatal d 30. An examination of Nissl-stained sections of the brains from developmentally hypothyroid offspring killed on postnatal d 23 revealed the presence of a heretofore unreported bilateral cellular malformation, a heterotopia, positioned within the white matter of the corpus callosum of both hemispheres. Immunohistochemical techniques were used to determine that this heterotopia primarily consists of neurons born between gestational d 17-19 and exhibits a dose-dependent increase in size with decreases in thyroid hormone levels. Importantly, this structural abnormality is evident at modest levels of maternal thyroid hormone insufficiency ( approximately 45% reductions in T(4) with no change in T(3)), persists in adult offspring despite a return to normal hormonal status, and is dramatically reduced in size with prenatal thyroid hormone replacement. Developmental exposure to methimazole, another goitrogen, also induced formation of this heterotopia. Whereas the long-term consequence of this cortical malformation on brain function remains to be determined, the presence of the heterotopia underscores the critical role thyroid hormone plays in brain development during the prenatal period and provides a new model in which to study mechanisms of cortical development and cortical dysplasia.

Topics: Agenesis of Corpus Callosum; Animals; Animals, Newborn; Brain Diseases; Cerebral Cortex; Congenital Hypothyroidism; Corpus Callosum; Disease Models, Animal; Female; Maternal Exposure; Phenylthiourea; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Rats; Rats, Long-Evans; Thyroid Hormones

Responses to a 5-min anoxia were studied in cats with different taste sensitivity for phenilthiocarbamide (PTC). The sensitive animals were more resistant against hypoxia. The difference in the cats seems to be determined by the condition of the cAMP system involved in adaptive responses.

Topics: Adaptation, Physiological; Animals; Brain Chemistry; Cats; Cyclic AMP; Disease Models, Animal; Hypoxia; Motor Cortex; Phenylthiourea; Taste; Time Factors

Topics: Animals; Antitubercular Agents; Cycloserine; Dapsone; Disease Models, Animal; Drug Synergism; Ethambutol; Ethionamide; Mice; Mycobacterium Infections; Phenylthiourea; Rabbits; Streptomycin; Thioacetazone