Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson's disease.

Abstract	L-DOPA-induced dyskinesia (LID) is one of the main limitations of long term L-DOPA use in Parkinson's disease (PD) patients. We show that chronic L-DOPA treatment induces novel dyskinetic behaviors in aphakia mouse with selective nigrostriatal deficit mimicking PD. The stereotypical abnormal involuntary movements were induced by dopamine receptor agonists and attenuated by antidyskinetic agents. The development of LID was accompanied by preprodynorphin and preproenkephalin expression changes in the denervated dorsal striatum. Increased FosB-expression was also noted in the dorsal striatum. In addition, FosB expression was noted in the pedunculopontine nucleus and the zona incerta, structures previously not examined in the setting of LID. The aphakia mouse is a novel genetic model with behavioral and biochemical characteristics consistent with those of PD dyskinesia and provides a more consistent, convenient, and physiologic model than toxic lesion models to study the mechanism of LID and to test therapeutic approaches for LID.
Authors	Yunmin Ding, Jacqueline Restrepo, Lisa Won, Dong-Youn Hwang, Kwang-Soo Kim, Un Jung Kang
Journal	Neurobiology of disease (Neurobiol Dis) Vol. 27 Issue 1 Pg. 11-23 (Jul 2007) ISSN: 0969-9961 [Print] United States
PMID	17499513 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antiparkinson Agents Enkephalins Fosb protein, mouse Protein Precursors Proto-Oncogene Proteins c-fos pre-prodynorphin Levodopa Dynorphins preproenkephalin
Topics	Afferent Pathways (pathology) Animals Antiparkinson Agents (pharmacology) Aphakia (complications, genetics) Corpus Striatum (pathology) Disease Models, Animal Dynorphins (genetics) Dyskinesia, Drug-Induced (complications, genetics) Enkephalins (genetics) Levodopa (pharmacology) Mice Mice, Inbred C57BL Mice, Neurologic Mutants Parkinsonian Disorders (complications, drug therapy, genetics, pathology) Protein Precursors (genetics) Proto-Oncogene Proteins c-fos (genetics) Substantia Nigra (pathology)

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