Short-Term Effects of Thyroid Hormones on Cytoskeletal Proteins Are Mediated by GABAergic Mechanisms in Slices of Cerebral Cortex from Young Rats

摘要

Thyroid hormones play important roles in brain function. However, few information is available about the effect of 3,5,3′-triiodo-l-thyronine (T3) or thyroxine (T4) on the in vitro phosphorylation of intermediate filament (IF) proteins from cerebral cortex of rats. In this study we investigated the involvement of GABAergic mechanisms mediating the effects of T3 and T4 on the in vitro incorporation of 32P into IF proteins from cerebral cortex of 10-day-old male rats. Tissue slices were incubated with or without T3, T4, γ-aminobutiric acid (GABA), kinase inhibitors or specific GABA antagonists and 32P-orthophosphate for 30 min. The IF-enriched cytoskeletal fraction was extracted in a high salt Triton-containing buffer and the in vitro 32P incorporation into IF proteins was measured. We first observed that 1 μM T3 and 0.1 μM T4 significantly increased the in vitro incorporation of 32P into the IF proteins studied through the PKA and PKCaMII activities. A similar effect on IF phosphorylation was achieved by incubating cortical slices with GABA. Furthermore, by using specific GABA antagonists, we verified that T3 induced a stimulatory effect on IF phosphorylation through noncompetitive mechanisms involving GABAA, beyond GABAB receptors. In contrast, T4 effects were mediated mainly by GABAB mechanisms. In conclusion, our results demonstrate a rapid nongenomic action of T3 and T4 on the phosphorylating system associated to the IF proteins in slices of cerebral cortex of 10 day-old male rats and point to GABAergic mechanisms mediating such effects.