Abnormal structure-specific peptide transmission and processing in a primate model of Parkinson's disease and l -DOPA-induced dyskinesia

Abstract A role for enhanced peptidergic transmission, either opioidergic or not, has been proposed for the generation of l -3,4-dihydroxyphenylalanine ( l -DOPA)-induced dyskinesia (LID) on the basis of in situ hybridization studies showing that striatal peptidergic precursor expression consistentl...

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Published in:Neurobiology of disease 2014-02, Vol.62, p.307-312
Main Authors: Bourdenx, Mathieu, Nilsson, Anna, Wadensten, Henrik, Fälth, Maria, Li, Qin, Crossman, Alan R, Andrén, Per E, Bezard, Erwan
Format: Article
Language:English
Subjects:
Animals
Antiparkinson Agents - toxicity
Dyskinesia, Drug-Induced - metabolism
Enkephalins - analysis
Enkephalins - metabolism
Female
Globus Pallidus - chemistry
Globus Pallidus - metabolism
L-DOPA-induced dyskinesia
Levodopa - toxicity
Life Sciences
Macaca
Macaca mulatta
Mass spectrometry
MPTP
Neurology
Neuropeptides - analysis
Neuropeptides - metabolism
Parkinson's disease
Parkinsonian Disorders - metabolism
Peptides
Primate
Primates
Protein Precursors - analysis
Protein Precursors - metabolism
Putamen - chemistry
Putamen - metabolism
Tachykinins - analysis
Tachykinins - metabolism
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Summary:Abstract A role for enhanced peptidergic transmission, either opioidergic or not, has been proposed for the generation of l -3,4-dihydroxyphenylalanine ( l -DOPA)-induced dyskinesia (LID) on the basis of in situ hybridization studies showing that striatal peptidergic precursor expression consistently correlates with LID severity. Few studies, however, have focused on the actual peptides derived from these precursors. We used mass-spectrometry to study peptide profiles in the putamen and globus pallidus (internalis and externalis) collected from 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine treated macaque monkeys, acutely or chronically treated with l -DOPA. We identified that parkinsonian and dyskinetic states are associated with an abnormal production of proenkephalin-, prodynorphin- and protachykinin-1-derived peptides in both segments of the globus pallidus. Moreover, we report that peptidergic processing is dopamine-state dependent and highly structure-specific, possibly explaining the failure of previous clinical trials attempting to rectify abnormal peptidergic transmission.
ISSN:0969-9961
1095-953X
1095-953X
DOI:10.1016/j.nbd.2013.10.016