DIFFERENTIAL EFFECT OF THYROID-HORMONE ON NGFI-A GENE-EXPRESSION IN DEVELOPING RAT-BRAIN

NGFI-A is an immediate early gene that is rapidly activated in quiesce nt cells by mitogens or in postmitotic neurons after depolarization. W e have previously shown that the expression of NGFI-A in the developin g rat brain is under the control of thyroid hormone. Now we report, by means of in situ hybridization histochemistry, the differential effec t of thyroid hormone on NGFI-A expression in distinct brain regions de pending on the developmental stage. NGFI-A messenger RNA (mRNA) conten t was analyzed in the piriform cortex, striatum, hippocampus, and cere bral cortex of control, hypothyroid, and T-3-injected hypothyroid rats at birth and on postnatal days 5 and 15. In the newborn rats, experim ental hypothyroidism is associated with reduced levels of NGFI-A mRNA in most of the brain regions studied. On postnatal day 15, the differe nce in NGFI-A expression between control and hypothyroid rats is less apparent in the striatum or no longer present in the piriform cortex a nd the hippocampus. In the cerebral cortex, hypothyroidism is associat ed with reduced levels of NGFI-A mRNA on postnatal day 15. The dentate gyrus is always insensitive to the thyroidal state. Administration of T-3 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 on ly 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 resul ted in an increased expression of the NGFI-A gene, which is of similar magnitude in control and hypothyroid rats.