Kainate treatment alters TGF-beta3 gene expression in the rat hippocampus.

In order to evaluate the role of transforming growth factor (TGF)-beta3 in the neurodegenerative process, we examined the levels of mRNA and immunocytochemical distribution for TGF-beta3 in the rat hippocampus after systemic kainic acid (KA) administration. Hippocampal TGF-beta3 mRNA level was reduced 3 h after KA injection. However, the levels of TGF-beta3 mRNA were elevated 1 day post-KA and lasted for at least 30 days. A mild TGF-beta3 immunoreactivity (TGF-beta3-IR) in the Ammon's horn and a moderate TGF-beta3-IR in the dentate granule cells were observed in the normal hippocampus. The CA1 and CA3 neurons lost their TGF-beta3-IR, while TGF-beta3-positive glia-like cells proliferated mainly throughout the CA1 sector and had an intense immunoreactivity at 7, 15 and 30 days after KA. This immunocytochemical distribution of TGF-beta3-positive non-neuronal populations was similar to that of glial fibrillary acidic protein (GFAP)-positive cells. Double labeling immunocytochemical analysis demonstrated colocalization of TGF-beta3- and GFAP-immunoreactivity in the same cells. These findings suggest a compensatory mechanism of astrocytes for the synthesis of TGF-beta3 protein in response to KA-induced neurodegeneration. In addition, exogenous TGF-beta3 (5 or 10 ng/i.c.v.) significantly attenuated KA-induced seizures and neuronal damages in a dose-related manner. Therefore, our results suggest that TGF-beta3 plays an important role in protective mechanisms against KA-induced neurodegeneration.