Consequence of nigrostriatal denervation and L-dopa therapy on the expression of glutamic acid decarboxylase messenger RNA in the pallidum.
To examine the consequences of nigrostriatal denervation and L-dopa treatment on the basal ganglia output system, we analyzed, by quantitative in situ hybridization, the messenger RNA coding for glutamic acid decarboxylase (Mr 67,000) (GAD67 mRNA) in pallidal cells from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) receiving or not receiving L-dopa, and their respective control subjects. In MPTP-treated monkeys, the expression of GAD67 mRNA was increased in cells from the internal pallidum, and this effect was abolished by L-dopa treatment. There were no differences in the levels of GAD67 mRNA between patients with PD, who were all treated with L-dopa, and control subjects. These results indicate that the level of GAD67 mRNA is increased in the cells of the internal pallidum after nigrostriatal dopaminergic denervation and that this increase can be reversed by L-dopa therapy.
Herrero
M T
MT
Department of Experimental Neurology, University of Navarra, Pamplona, Spain.
Levy
R
R
Ruberg
M
M
Luquin
M R
MR
Villares
J
J
Guillen
J
J
Faucheux
B
B
Javoy-Agid
F
F
Guridi
J
J
Agid
Y
Y
Obeso
J A
JA
Hirsch
E C
EC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry*; D005968:Glutamate Decarboxylase / Q000737:chemistry*; D006801:Humans; D017403:In Situ Hybridization; D007980:Levodopa / Q000627:therapeutic use*; D008252:Macaca fascicularis; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000188:drug therapy; D012333:RNA, Messenger / Q000032:analysis*; D013378:Substantia Nigra / Q000187:drug effects*
D012333:RNA, Messenger; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005968:Glutamate Decarboxylase