Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man.
The present study was performed to determine the effect of a nearly complete nigrostriatal dopaminergic denervation on DARPP-32 levels in the striatum from animals and parkinsonian patients. DARPP-32 levels were estimated by in vitro phosphorylation in the presence of cAMP, or after inactivation of endogenous kinases and phosphatases, in the presence of the catalytic subunit of cAMP-dependent protein kinase. Intranigral 6-hydroxydopamine (6-OHDA) infusion in rats, or peripheral administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets, did not change striatal DARPP-32 levels. Postmortem studies, carried out on brains obtained shortly after death, from patients with Parkinson disease, or from patients with progressive supranuclear palsy, showed that the levels of striatal DARPP-32 were not different from controls. These results indicate that dopaminergic striatal denervation did not modify the amount of DARPP-32 in the striatum, suggesting that the expression of DARPP-32, a protein which mediates some of the effects of dopamine in striatal neurons, is independent from the dopaminergic innervation.
Raisman-Vozari
R
R
INSERM U 289, CHU Pitié-Salpêtrière, Paris, France.
Girault
J A
JA
Moussaoui
S
S
Feuerstein
C
C
Jenner
P
P
Marsden
C D
CD
Agid
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002143:Callitrichinae; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D051381:Rats; D013378:Substantia Nigra / Q000502:physiology*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D004298:Dopamine