Differential effect of thyroid hormone on NGFI-A gene expression in developing rat brain

Abstract

NGFI-A is an immediate early gene that is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. We have previously shown that the expression of NGFI-A in the developing rat brain is under the control of thyroid hormone. Now we report, by means of in situ hybridization histochemistry, the differential effect of thyroid hormone on NGFI-A expression in distinct brain regions depending on the developmental stage. NGFI-A messenger RNA (mRNA) content was analyzed in the piriform cortex, striatum, hippocampus, and cerebral cortex of control, hypothyroid, and T3-injected hypothyroid rats at birth and on postnatal days 5 and 15. In the newborn rats, experimental hypothyroidism is associated with reduced levels of NGFI-A mRNA in most of the brain regions studied. On postnatal day 15, the difference in NGFI-A expression between control and hypothyroid rats is less apparent in the striatum or no longer present in the piriform cortex and the hippocampus. In the cerebral cortex, hypothyroidism is associated with reduced levels of NGFI-A mRNA on postnatal day 15. The dentate gyrus is always insensitive to the thyroidal state. Administration of T3 accelerates the recovery of NGFI-A mRNA in 5- and 15-day-old rats. However, in newborn rats, the effect of the hormone is noticeable only in the piriform cortex. We also show that the reduced level of NGFI-A mRNA in hypothyroidism is accompanied by a reduction in the protein level. Convulsions induced by pentylenetetrazole administration resulted in an increased expression of the NGFI-A gene, which is of similar magnitude in control and hypothyroid rats.