Differential gene expression induced by chronic levodopa treatment in the striatum of rats with lesions of the nigrostriatal system.
Levodopa, the major treatment for patients with Parkinson's disease, has been shown to induce a variety of compensatory effects, including facilitation of sprouting by dopaminergic neurons, in experimental animals with lesions leading to denervation of the striatum. To better understand the cellular and molecular environment where most of these compensatory changes take place, in particular elements that might contribute to the recovery of dopaminergic innervation, we have constructed a differential expression library enriched in transcripts from the striata of rats with lesions of the medial forebrain bundle treated with levodopa for 6 months. We have used this library to screen an expression array of rat genes representing the major cell functions, and have identified several that are involved in neurotrophic mechanisms and plasticity. We have confirmed the differential expression of selected transcripts by non-radioactive in situ hybridization, and report that the growth factor pleiotrophin, myelin basic protein and calmodulin are overexpressed in the denervated striatum of levodopa-treated rats.
Ferrario
Juan E
JE
Instituto de Investigaciones Farmacológicas (ININFA), UBA-CONICET, Buenos Aires, Argentina. ferrario@ffyb.uba.ar
Taravini
Irene R E
IR
Mourlevat
Sophie
S
Stefano
Andrea
A
Delfino
Marina A
MA
Raisman-Vozari
Rita
R
Murer
M Gustavo
MG
Ruberg
Merle
M
Gershanik
Oscar
O
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000293:injuries / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D015723:Gene Library; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007980:Levodopa / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism*
D000978:Antiparkinson Agents; D002147:Calmodulin; D002352:Carrier Proteins; D016207:Cytokines; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C066845:pleiotrophin; D007980:Levodopa; D016627:Oxidopamine