Striatal leucine-rich repeat kinase 2 mRNA is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned common marmosets (Callithrix jacchus) with L-3, 4-dihydroxyphenylalanine methyl ester-induced dyskinesia.
The level of leucine-rich repeat kinase 2 (Lrrk2) mRNA expression was measured by reverse transcription-polymerase chain reaction in anterior striatum from normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets (Callithrix jacchus) that had L-3,4-dihydroxyphenylalanine methyl ester (L-DOPA)-induced dyskinesia. The level of striatal Lrrk2 mRNA was increased in MPTP-treated common marmosets that had L-DOPA-induced dyskinesia compared with normal animals that did not receive l-DOPA. Marmosets that exhibited higher levels of dyskinesia had the greatest increase in striatal Lrrk2 mRNA. Lrrk2 mRNA expression was also measured in human striatum and substantia nigra from control subjects and patients dying with Parkinson's disease. In contrast to marmoset tissue, no alteration in Lrrk2 mRNA expression was found in parkinsonian human brain. However, the brain was from patients who had an overall low level of dyskinesia. The correlation between striatal Lrrk2 mRNA levels in MPTP-treated common marmoset striatum and L-DOPA-induced dyskinesia indicates that LRRK2 may have a role in the molecular alterations that cause L-DOPA-induced dyskinesia.
Hurley
M J
MJ
Neurodegenerative Diseases Research Group, Pharmaceutical Sciences Research Division, School of Biomedical and Health Sciences, King's College, London SE1 1UL, UK. michael.j.hurley@kcl.ac.uk
Patel
P H
PH
Jackson
M J
MJ
Smith
L A
LA
Rose
S
S
Jenner
P
P
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000978:Antiparkinson Agents / Q000633:toxicity*; D002144:Callithrix; D003627:Data Interpretation, Statistical; D015259:Dopamine Agents; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000633:toxicity*; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000378:metabolism
D000199:Actins; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D012333:RNA, Messenger; D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases