EARLY EFFECTS OF FGF-2 ON GLIAL-CELLS IN THE MPTP-LESIONED STRIATUM

Fibroblast growth factor-2 (FGF-2), locally administered in gelfoam to the striatum of mice treated with the neurotoxic drug 1-methyl-4-phen yl-1,2,3,6-tetrahydropyridine (MPTP), has restorative and neuroprotect ive effects on dopaminergic neurons and associated striatal transmitte r systems. Most of the beneficial alterations are apparently indirect. FGF-2 must therefore act through a series of cellular and molecular i ntermediate steps, which have not been explored. We have previously sh own that FGF-2 does not significantly affect the astroglial reaction a t the time, when the neuroprotective effect of FGF-2 reaches a peak (D ay 11). In this study we have investigated the effect of FGF-2 at earl ier time points after MPTP treatment. We report now that as early as 6 h after administration of the gelfoam containing either FGF-2 or cont rol protein, FGF-2 immunoreactivity disappears from astroglial nuclei, while appearing in small ramified GFAP- and S-100-negative cells, mos t likely microglia. At 18 h, numbers and staining intensities of GFAP- ir astroglial cells are greater in FGF-2- than in cytochrome C-treated animals. At this time FGF-2-ir reappears in astroglia nuclei of cytoc hrome C-treated animals, but remains undetectable in the striatum carr ying the FGF-2-containing gelfoam. Ramified GFAP/S-100-negative presum ed microglial cells are now intensely ir for FGF-2. Signs of an FGF-2- mediated astrogliotic reaction are very pronounced at 18 h and 2 days, but no longer at 11 days, when the astrogliosis reaction has become e qually strong in FGF-2- and cytochrome C-treated striata. Our results suggest that administration of FGF-2 to the MPTP-lesioned striatum has early effects on astro- and presumed microglia cells, notably on the nuclear FGF-2-ir of astrocytes. These changes may be involved in media ting the neuroprotective effects of FGF-2 in the MPTP-model of Parkins onism. (C) 1996 Academic Press, Inc.