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

Mathieu Bourdenx, Anna Nilsson, Henrik Wadensten, Maria Fälth, Qin Li, Alan R. Crossman, Per E. Andrén, Erwan Bezard
Neurobiology of Disease. 2014-02-01; 62: 307-312
DOI: 10.1016/j.nbd.2013.10.016

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1. Neurobiol Dis. 2014 Feb;62:307-12. doi: 10.1016/j.nbd.2013.10.016. Epub 2013 Oct
19.

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

Bourdenx M(1), Nilsson A(2), Wadensten H(2), Fälth M(2), Li Q(3), Crossman AR(4),
Andrén PE(2), Bezard E(5).

Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France.
(2)Department of Pharmaceutical Biosciences, Biomolecular Imaging and Proteomics,
Uppsala University, Box 591, SE-75124 Uppsala, Sweden.
(3)Motac Neuroscience, Manchester, UK; Institute of Laboratory Animal Sciences,
China Academy of Medical Sciences, Beijing, China.
(4)Motac Neuroscience, Manchester, UK.
(5)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
Bordeaux, France; Motac Neuroscience, Manchester, UK; Institute of Laboratory
Animal Sciences, China Academy of Medical Sciences, Beijing, China. Electronic
address: .

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.

© 2013.

DOI: 10.1016/j.nbd.2013.10.016
PMID: 24148855 [Indexed for MEDLINE]

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