MODULATION OF MESSENGER-RNA EXPRESSION OF THE NEUROTROPHINS OF THE NERVE GROWTH-FACTOR FAMILY AND THEIR RECEPTORS IN THE SEPTUM AND HIPPOCAMPUS OF RATS AFTER TRANSIENT POSTNATAL THYROXINE TREATMENT - 1 - EXPRESSION OF NERVE GROWTH-FACTOR, BRAIN-DERIVED NEUROTROPHIC FACTOR, NEUROTROPHIN-3, AND NEUROTROPHIN-4 MESSENGER-RNA

Early postnatal application of thyroid hormones to rats results in mor phological changes in septum and hippocampus. Modulation in the expres sion of either neurotrophins and/or their receptors is postulated to b e responsible for these effects. In the present study we tested whethe r thyroxine administration leads to changes in the expression of neuro trophins of the nerve growth factor (NGF) family. Newborn rats were tr eated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the r everse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) level s. In hippocampus of hyperthyroid rats, as compared to controls, we fo und higher levels of BDNF and NT-3 mRNA over the total investigation p eriod, whereas in the septum a thyroxine-dependent increase in NT-3 mR NA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) a t particular postnatal days. From these data we conclude that modulati on of neurotrophin expression is a possible mechanism for the morpholo gical modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.