Effect of hypothyroidism on the expression of three microtubule-associated proteins (1A, 1B and 2) in developing rat cerebellum.

The microtubule-associated proteins 1A, 1B and 2 are present at high levels in Purkinje cell dendrites of normal adult rat cerebellum but show characteristic changes in localization during cerebellar development that allow examination of the effects of hypothyroidism on the development of both Purkinje cells and granule cells. Neonatal rats were made hypothyroid by treatment with propylthiouracil from the day of birth (post-natal day 0, P0). The expression of the microtubule-associated proteins 1A, 1B and 2 in the cerebellum of hypothyroid animals was examined using immunocytochemical techniques and compared to the normal developmental pattern in control animals. The normal developmental decrease in microtubule-associated protein 1A and 1B levels in parallel fibres was delayed in the cerebellum of hypothyroid animals and these proteins persisted in parallel fibres until after P20. Microtubule-associated protein 1B but not 1A was still present in parallel fibres in less mature folia at P30 in hypothyroid rats suggesting that the expression of these two microtubule-associated proteins is regulated separately. In the molecular layer staining with anti-microtubule-associated protein 2 was enriched in Purkinje cell dendrites in normal and hypothyroid cerebella and the stained Purkinje cell dendrites in hypothyroid cerebellum demonstrated a typical deformed morphology at P15. The results show that the restricted subcellular localization of these microtubule-associated proteins is maintained in the cerebellum of hypothyroid rats but the developmental changes in their expression are delayed.