SPLICING OF JUVENILE AND ADULT TAU-MESSENGER RNA VARIANTS IS REGULATED BY THYROID-HORMONE

The effect of thyroid hormone on the expression of tau transcripts was studied during postnatal brain development. The level of tau mRNA was only slightly changed postnatally in the cerebral hemispheres of hypothyroid rats, whereas the level of tau mRNA in the cerebellum was maintained at a higher level than in the euthyroid controls. As shown by in situ hybridization studies, such an alteration in tau mRNA expression can be ascribed to an effect of thyroid hormone on the rate of migration of the granule cells in the cerebellum; that tau mRNAs remain high in the cerebellum as long as the granule cells are migrating correlates with the observation that hypothyroidism slows the rate of migration of granule cells. RNase protection assays also showed that thyroid hormone deficiency delays the transition between the immature and mature tau transcripts in both brain regions. Thus, one of the effects of thyroid hormone is to regulate the splicing mechanism that allows replacement of the juvenile tau variants by the adult entities during neuronal differentiation.