Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson's disease.
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.
Ding
Yunmin
Y
Department of Neurology, University of Chicago, Chicago, IL 60637, USA.
Restrepo
Jacqueline
J
Won
Lisa
L
Hwang
Dong-Youn
DY
Kim
Kwang-Soo
KS
Kang
Un Jung
UJ
D000344:Afferent Pathways / Q000473:pathology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001035:Aphakia / Q000150:complications / Q000235:genetics*; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D004399:Dynorphins / Q000235:genetics; D004409:Dyskinesia, Drug-Induced / Q000150:complications / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D020734:Parkinsonian Disorders / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D013378:Substantia Nigra / Q000473:pathology
D000978:Antiparkinson Agents; D004745:Enkephalins; C483819:Fosb protein, mouse; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; C036448:pre-prodynorphin; D007980:Levodopa; D004399:Dynorphins; C033660:preproenkephalin