Sequential Administration of GDNF into the Substantia Nigra and Striatum
Promotes Dopamine Neuron Survival and Axonal Sprouting but Not Striatal
Reinnervation or Functional Recovery in the Partial 6-OHDA Lesion Model.
Glial cell line-derived neurotrophic factor (GDNF) has
prominent survival-promoting effects on lesioned
nigrostriatal dopamine neurons, but understanding of the
conditions under which functional recovery can be obtained
remains to be acquired. We report here the time course of
nigrostriatal axon degeneration in the partial lesion
model of Parkinson's disease and the morphological and
functional effects of sequential administration of GDNF in
the substantia nigra (SN) and striatum during the first 5
weeks postlesion. By 1 day postlesion, the nigrostriatal
axons had retracted back to the level of the caudal globus
pallidus. Over the next 6 days axonal retraction
progressed down to the SN, and during the following 7
weeks 74% of tyrosine hydroxylase-positive (TH(+)) and 84%
of retrogradely labeled nigral neurons were lost, with a
more pronounced loss in the rostral part of the SN. GDNF
administration protected 70 and 72% of the nigral TH(+)
and retrogradely labeled cell bodies, respectively, but
did not prevent the die-back of the lesioned nigrostriatal
axons. Although clear signs of sprouting were observed
close to the injection site in the striatum as well as in
the globus pallidus, the overall DA innervation of the
striatum [as measured by
[(3)H]-N-[1- (2-benzo(b) thiopenyl) cyclohexyl] piperidine-binding
autoradiography] was not improved by the GDNF treatment.
Moreover, the lesion-induced deficits in forelimb akinesia
and drug-induced rotation were not attenuated. We conclude
that functional recovery in the partial lesion model
depends not only on preservation of the nigral cell
bodies, but more critically on the ability of GDNF to
promote significant reinnervation of the denervated
striatum. Copyright 2000 Academic Press.
Exp Neurol 2000 Feb;161(2):503-516
Rosenblad C, Kirik D, Bjorklund A
Department of Physiology and Neuroscience, Lund University, Solvegatan 17, Lund, S-223 62, Sweden
PMID: 10686072
<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10686072&dopt=Abstract>
janet paterson
52 now / 41 dx / 37 onset
a new voice: http://www.geocities.com/janet313/
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0
