Meeting Abstract

12.9  Thursday, Jan. 3  Stress regulation of basic transcription element binding protein-1 (BTEB1) in Xenopus laevis and its implications for vertebrate neuroplasticity. BONETT, Ronald, M*; HU, Fang; DENVER, Rober, J; Univ. of Michigan; Univ. of Michigan; Univ. of Michigan ron-bonett@utulsa.edu

Basic transcription element binding protein 1 (BTEB1; or Kr�ppel-like factor 9) is a thyroid hormone-induced immediate early gene implicated in neural development and plasticity in vertebrates. We analyzed the regulation of BTEB1 gene expression by stress and corticosterone (CORT) in Xenopus laevis. Frogs exposed to a shaking stressor for 4 hr exhibited an increase in plasma [CORT] and an increase in BTEB1 protein in the preoptic area (POa) and the optic tectum (OT). We also found that in tissue culture cells of X. laevis origin (XtC2) exposure to CORT caused a rapid (by 30 minutes) and robust (15 fold) increase in BTEB1 mRNA, suggesting that CORT can directly regulate the BTEB1 gene. The action of CORT on BTEB1 in XtC2 cells was completely blocked by the glucocorticoid receptor (GR) antagonist RU486. Similarly, juvenile X. laevis injected with CORT or subjected to 4 hr shaking stress showed significant elevations in BTEB1 mRNA in the POa and diencephalon (including the OT), and the stressor-dependent gene induction was blocked by pretreatment with RU486. We conclude that in frogs, stress induces BTEB1 gene expression and this is dependent on the elevation of plasma CORT. Furthermore, our findings suggest that CORT action is mediated by the GR, and that BTEB1 is a direct GR target gene. Given that BTEB1 is known to influence neuronal morphology, we hypothesize that this transcription factor functions as an intermediary in the actions of stress hormones on brain gene expression and the expression of neuroplasticity. (Supported by NIH grant 1 R01 NS046690 and NSF grant IBN 0235401 to R.J.D.)