Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning.
European Journal of Neuroscience. 2005-07-01; 22(1): 283-287
DOI: 10.1111/j.1460-9568.2005.04196.x
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1. Eur J Neurosci. 2005 Jul;22(1):283-7.
Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the
extent and pattern of nigrostrial lesioning.
Guigoni C(1), Dovero S, Aubert I, Li Q, Bioulac BH, Bloch B, Gurevich EV, Gross
CE, Bezard E.
Author information:
(1)Laboratoire de Physiologie et Physiopathologie de la Signalization Cellulaire,
CNRS UMR 5543, Universite victor Segalen-Bordeaux, 33076 Bordeaux Cedex, France.
The extent of nigrostriatal denervation is presumed to play a role in the genesis
of levodopa-induced dyskinesia. Yet some parkinsonian patients who have been
treated over a long period do not develop dyskinesia, raising the possibility
that the pattern of denervation is as important as the extent of lesioning as a
risk factor. Here we study the extent and pattern of nigrostriatal denervation in
a homogeneous population of parkinsonian macaque monkeys chronically treated with
levodopa. Based on the characteristics of the lesioning, non-dyskinetic animals
could not be differentiated from those with dyskinesia. Indeed, the number of
tyrosine-hydroxylase (TH)-immunopositive neurons in the substantia nigra pars
compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as
well as the overall TH striatal content measured by Western blotting were
identical. Moreover, the patterns of lesioning assessed by a detailed analysis of
the TH- and DAT-immunopositive striatal fibers were comparable in all functional
quadrants and at all rostro-caudal levels considered. These data indicate that
neither the extent nor the pattern of nigrostriatal lesioning are sufficient to
explain the occurrence of levodopa-induced dyskinesia.
DOI: 10.1111/j.1460-9568.2005.04196.x
PMID: 16029219 [Indexed for MEDLINE]