PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease.
PET and: markers for the pre- and postsynaptic neurons were used to study the dopamine system in vivo in Huntington's disease. The radioligands used were [11C]SCH 23390 for D1-receptors, [11C]raclopride for D2-receptors and [11C]beta-CIT for dopamine transporters. Five patients with Huntington's disease and five matched controls were recruited. Brain anatomy was examined by MRI. The findings in patients were as follows. Postsynaptic D1- and D2-receptor densities were similarly reduced in the striatum. A reduction in D1-receptor density was shown in the temporal cortex; it draws attention to the cortical degeneration in relation to the cognitive deficits observed in Huntington's disease. The reduction of D1- and D2-receptor binding potentials in the striatum correlated significantly with increasing duration of illness. The correlation between the duration of illness and decline of D1- and D2-receptors make these receptors valuable as quantitative markers for the Huntington's disease degenerative process. Besides postsynaptic changes, a significant 50% decrease of [11C]beta-CIT binding to the dopamine transporter was found in the striatum. A reduced striatal blood flow in Huntington's disease cannot be excluded and could account for a small part of the decrease in [11C]beta-CIT binding. We suggest that the finding reflects a loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease.
Ginovart
N
N
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lundin
A
A
Farde
L
L
Halldin
C
C
Bäckman
L
L
Swahn
C G
CG
Pauli
S
S
Sedvall
G
G
D000328:Adult; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017661:Receptors, Presynaptic; D012457:Salicylamides; D020891:Raclopride; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine