Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning

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 o...

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Vydané v:	The European journal of neuroscience Ročník 22; číslo 1; s. 283 - 287
Hlavní autori:	Guigoni, Céline, Dovero, Sandra, Aubert, Incarnation, Li, Qin, Bioulac, Bernard H., Bloch, Bertrand, Gurevich, Eugenia V., Gross, Christian E., Bezard, Erwan
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Oxford, UK Blackwell Science Ltd 01.07.2005
Predmet:	Animals Antiparkinson Agents - adverse effects Cell Count Cell Death - drug effects Cell Death - physiology Corpus Striatum - metabolism Corpus Striatum - pathology Corpus Striatum - physiopathology Disease Models, Animal Dopamine - metabolism Dopamine Plasma Membrane Transport Proteins dopamine transporter Dyskinesia, Drug-Induced - pathology Dyskinesia, Drug-Induced - physiopathology Female Immunohistochemistry Levodopa - adverse effects Macaca fascicularis Membrane Glycoproteins - metabolism Membrane Transport Proteins - metabolism Nerve Degeneration - chemically induced Nerve Degeneration - pathology Nerve Degeneration - physiopathology Nerve Tissue Proteins - metabolism Neural Pathways - metabolism Neural Pathways - pathology Neural Pathways - physiopathology Neurons - metabolism Neurons - pathology Parkinson's disease Parkinsonian Disorders - drug therapy Parkinsonian Disorders - pathology Parkinsonian Disorders - physiopathology striatum substantia nigra Substantia Nigra - metabolism Substantia Nigra - pathology Substantia Nigra - physiopathology Tyrosine 3-Monooxygenase - metabolism tyrosine hydroxylase
ISSN:	0953-816X, 1460-9568
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Shrnutí:	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.
Bibliografia:	istex:58BB6F6D34CE632A84E4B6186BEF91480ACEDCE4 ArticleID:EJN4196 ark:/67375/WNG-R9Q52NBS-H ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0953-816X 1460-9568
DOI:	10.1111/j.1460-9568.2005.04196.x