Motor coordination is partially impaired in neonatal mice with moderate hypothyroidism but not with mild hypothyroidism

Abstract

Thyroid hormones regulate metabolism in various organs and brain development. Severe form of congenital hypothyroidism causes growth retardation and intellectual disability. However, neuronal phenotypes caused by mild or moderate perinatal hypothyroidism have not yet been fully studied. To evaluate the effect of mild or moderate perinatal hypothyroidism on early development of postnatal mice, we induced hypothyroidism by administering propylthiouracil (PTU) during the perinatal period, from embryonic day 14 to postnatal day (PND) 21. We examined the motor coordination of newborns and vestibular function from PND 3 to PND 21. Animals in the moderate hypothyroid (50 ppm PTU-administered) group showed impaired motor coordination by a righting reflex test and a rotarod test, whereas animals in the mild hypothyroid (5 ppm PTU-administered) group showed normal motor coordination. Hypothyroidism did not affect vestibular function. Then, we measured mRNA and protein levels of glutamate receptor subunits in the cerebellum in developmental period. The levels of AMPA receptor subunit ｍRNA were altered initially, followed by alteration of NMDA receptor subunit mRNA in the later period. On the other hand, protein level has changed only in AMPA receptor subunit 1 (GluA1) on PND 8. These results indicate that moderate perinatal hypothyroidism impairs motor coordination during early postnatal development. The altered protein level of GluA1 in the cerebellum may be involved in such impairments.