Adult Rat Brain Is Sensitive to Thyroid Hormone Regulation of RC3 / Neurogranin mRNA

The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods " of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Mufioz, A., A. Rodriguez-Pefia, A. Perez-Castillo, B. Ferreiro, J. G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a re-versible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a de-creased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypo-thyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in ei-ther experimental situation. RC3 mRNA levels were not af-fected by food restriction demonstrating that the effect of hypo-thyroidism was not related to the lack of weight gain. The con-trol of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations in-duced by hypothyroidism in the adult brain. (J. Clin. Invest