Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia.
We have examined the pattern of striatal messenger RNA expression of over 8000 genes in a rat model of levodopa (L-DOPA)-induced dyskinesia and Parkinson disease (PD). 6-Hydroxydopamine (6-OHDA)-lesioned rats were treated with L-DOPA or physiological saline for 22 days and repeatedly tested for antiakinetic response to L-DOPA and the development of abnormal involuntary movements (AIMs). In a comparison of rats that developed a dyskinetic motor response to rats that did not, we found striking differences in gene expression patterns. In rats that developed dyskinesia, GABA neurons had an increased transcriptional activity, and genes involved in Ca2+ homeostasis, in Ca2+ -dependent signaling, and in structural and synaptic plasticity were upregulated. The gene expression patterns implied that the dyskinetic striatum had increased transcriptional, as well as synaptic activity, and decreased capacity for energy production. Some basic maintenance chores such as ribosome protein biosynthesis were downregulated, possibly a response to expended ATP levels.
Konradi
Christine
C
Laboratory of Neuroplasticity, McLean Hospital, Belmont, MA 02478, USA. konradi@mclean.harvard.edu
Westin
Jenny E
JE
Carta
Manolo
M
Eaton
Molly E
ME
Kuter
Katarzyna
K
Dekundy
Andrzej
A
Lundblad
Martin
M
Cenci
M Angela
MA
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D003342:Corpus Striatum / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D015259:Dopamine Agents; D004409:Dyskinesia, Drug-Induced / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D006706:Homeostasis; D007477:Ions; D007980:Levodopa; D008840:Microfilament Proteins / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology; D005810:Multigene Family; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics; D013569:Synapses
D002352:Carrier Proteins; D015259:Dopamine Agents; D007477:Ions; D008840:Microfilament Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D007980:Levodopa; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D000252:Calcium-Transporting ATPases