Difluoromethylornithine counteracts lesion-induced astrogliosis in rat hippocampus: enhancement of inhibitory effect by combined treatment with GM1 ganglioside

Abstract

The effect of difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine biosynthesis, and its combined action with GM1 ganglioside, was studied on the GFAP content in a model of remote astrogliosis evoked in the hippocampus by lateral fimbria transection. DFMO markedly suppressed hippocampal gliosis as measured by GFAP immunoblotting seven days postsurgery. Combined treatment with DFMO and GM1 ganglioside - a substance which alone also counteracts hippocampal gliosis, produced a stronger suppressive effect than DFMO. The results support the hypothesis of a causal link between lesion induced events: polyamine biosynthesis and astroglial reaction. Potentiation of the inhibitory effect of DFMO by GM1 ganglioside suggests that the latter does not act through the mechanism involving ODC suppression.