Journal of Neuroscience, Vol 10, 1912-1921, Copyright © 1990 by Society for Neuroscience
Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice
D Otto and K Unsicker
Philipps-University, Department of Anatomy and Cell Biology, Marburg, Federal Republic of Germany.
The specific mechanisms underlying the restorative effects of adrenal
chromaffin grafts in experimental parkinsonism are still obscure. Recent
findings indicated an involvement of graft-induced trophic interactions in
the course of recovery-related events. Evidence that basic fibroblast
growth factor (bFGF), a potent trophic protein for neurons, (1) is present
in chromaffin cells (Blottner et al., 1989) and (2) exerts trophic
activities on embryonic mesencephalic neurons in vitro (Ferrari et al.,
1989) provided the rationale for administering bFGF in gel foam implants
unilaterally to the striatum of 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned mice. Simultaneous
bFGF/MPTP treatment diminished bilaterally the reduction of striatal
dopamine (DA) levels observed in cytochrome c/MPTP-treated mice and led to
an ipsilateral reappearance of tyrosine hydroxylase (TH)-like
immunoreactive fibers, most notably adjacent to the implant, 2 weeks after
the surgery. Determinations of TH activities and TH immunoblotting
demonstrated that bFGF almost fully reversed the loss of TH activity on
either side but restored TH protein more on the ipsilateral than on the
contralateral side. Furthermore, differences in dihydroxyphenylacetic acid
levels, which were about twice as high on the contralateral side yet still
reduced with respect to untreated mice, supported our assumption that the
molar TH activity was increased on the untreated side, possibly due to an
intrinsic compensatory up- regulation. Delayed administration of bFGF
starting 8 d after the MPTP treatment was equally effective with regard to
morphological parameters. Our results suggest that bFGF partially prevents
the deleterious chemical and morphological consequences of an MPTP-mediated
nigrostriatal lesion. Thus, bFGF mimics at least the morphological effects
of chromaffin cell grafts to the MPTP-lesioned brain.
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