Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia.

Konradi C, Westin JE, Carta M, Eaton ME, Kuter K, Dekundy A, Lundblad M, Cenci MA
Neurobiol Dis. 2004 17 (2): 219-36

PMID: 15474360 · PMCID: PMC4208672 · DOI:10.1016/j.nbd.2004.07.005

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.

MeSH Terms (25)

Animals Calcium-Transporting ATPases Carrier Proteins Corpus Striatum Cytoskeleton Dopamine Agents Dyskinesia, Drug-Induced Energy Metabolism Gene Expression Gene Expression Profiling Homeostasis Ions Levodopa Microfilament Proteins Mitochondria Multigene Family Neurotransmitter Agents Oligonucleotide Array Sequence Analysis Phosphoric Monoester Hydrolases Phosphotransferases Rats Rats, Sprague-Dawley Receptors, Cell Surface RNA, Messenger Synapses

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