Administration of thyroid hormone increases reelin and brain-derived neurotrophic factor expression in rat hippocampus in vivo

Thyroid hormones play important roles in the maturation and function of the central nervous system. However, the underlying mechanism behind thyroid hormone-regulated gene expression in the adult brain is not well understood. Two genes critical for neuronal plasticity and implicated in psychiatric disorders, reelin and brain-derived neurotrophic factor (BDNF), were investigated in the present study. Triiodothyronine (T3), the active form of thyroid hormone was administered to young adult rats in two different manners: systemic injection or local brain infusion. Real time RT-PCR results revealed that T3 administration lead to a significant increase in reelin, total BDNF and exon-specific BDNF mRNA expression in the hippocampus. Furthermore, the association of transcriptional coactivators (including steroid receptor coactivator-1 (SRC-1), cAMP response element binding protein-binding protein (CBP), and thyroid hormone receptor associated protein 220 (TRAP 220)) and RNA polymerase II (RNA Pol II), with reelin and BDNF genes in the rat hippocampus displayed a distinct process following thyroid hormone administration. These findings suggest that association of transcriptional coactivators and RNA Pol II with gene promoters may be a possible mechanism explaining T3-induced reelin and BDNF expression in the hippocampus of young adult rats. (C) 2009 Elsevier B.V. All rights reserved.