DIFLUOROMETHYLORNITHINE COUNTERACTS LESION-INDUCED ASTROGLIOSIS IN RAT HIPPOCAMPUS - ENHANCEMENT OF INHIBITORY EFFECT BY COMBINED TREATMENTWITH GM1 GANGLIOSIDE

The effect of difluoromethylornithine (DFMO), an irreversible inhibito r of ornithine decarboxylase (ODC), the rate limiting enzyme of polyam ine biosynthesis, and its combined action with GM1 ganglioside, was st udied on the GFAP content in a model of remote astrogliosis evoked in the hippocampus by lateral fimbria transection. DFMO markedly suppress ed hippocampal gliosis as measured by GFAP immunoblotting seven days p ostsurgery. Combined treatment with DFMO and GM1 ganglioside - a subst ance which alone also counteracts hippocampal gliosis, produced a stro nger 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 DFM O by GM1 ganglioside suggests that the latter does not act through the mechanism involving ODC suppression.