Abstract
Thyroid hormone (T(3)) plays an essential role in the central nervous system development. Astrocytes mediate many of the T(3) effects in the growth and differentiation of cerebellum. In culture, T(3) induces cerebellar astrocytes to secrete growth factors, mainly FGF(2), and alters the expression and organization of the extracellular matrix (ECM) proteins, laminin, and fibronectin. In addition, T(3)-treated astrocytes promote neuronal differentiation. In this study, we have investigated whether other ECM molecules, such as syndecans, are involved in T(3) action. Thus, we analyzed the expression of syndecans (1-4) by RT-PCR in astrocyte cultures from cerebellum, cortex, and hippocampus of newborn rats. Our results showed that syndecans (1-4) are expressed in astrocytes of cerebellum and cortex, whereas in hippocampus only syndecans 2 and 4 were detected. Semi-quantitative RT-PCR analysis revealed the reduced expression of syndecans 1, 2, and 4, and increased expression of syndecan 3 in hypothyroid cerebellum, when compared to the euthyroid tissue. Furthermore, we observed a reduced expression of syndecans 2 and 3 in T(3)-treated cerebellar astrocytes, when compared to control cultures. This balance of proteoglycans may be involved in T(3) action mediated by FGF(2) signaling, possibly affecting the formation of the trimeric signaling receptor complex composed by syndecan/FGF/FGF-receptor (FGFR), which is essential for FGFR dimerization, activation, and subsequent cell signaling.