Experimental parkinsonism modulates multiple genes involved in the transduction of dopaminergic signals in the striatum.
The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats.
Napolitano
Maddalena
M
Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Rome, Italy.
Centonze
Diego
D
Calce
Angelica
A
Picconi
Barbara
B
Spiezia
Stefania
S
Gulino
Alberto
A
Bernardi
Giorgio
G
Calabresi
Paolo
P
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D003714:Denervation; D004298:Dopamine / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics*
D016627:Oxidopamine; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine