Effect of age on markers for monoaminergic neurons of normal and MPTP-lesioned rhesus monkeys: a multi-tracer PET study.
The binding of three tracers for monoaminergic terminals was mapped in the brain of healthy young (N=6) and healthy old rhesus monkeys (N=4), aged monkeys with mild unilateral intracarotid MPTP lesions (N=3), and monkeys of intermediate age with severe systemic MPTP lesions (N=6). The ligand for monoaminergic vesicles (+)-[(11)C]dihydrotetrabenazine (+DTBZ) had a mean binding potential (pB) of 1.4 in striatum of the healthy young monkeys, which was reduced by 20% in putamen of the old monkeys. The catecholamine transporter ligand (+)-[(11)C]methylphenidate (+MP) had a mean pB of 1.3 in striatum of the young monkeys, which was reduced by 40% in caudate and putamen of the old monkeys. The DOPA decarboxylase substrate [(18)F]fluoro-l-DOPA (FDOPA) had a mean decarboxylation coefficient (k(3)(S)) of 0.4 h(-1) in striatum of the young group, and was not significantly reduced in the aged group. Of the three ligands, only +DTBZ pB was significantly reduced in striatum of the small group of animals with mild unilateral lesions. In the group with systemic MPTP lesions, the mean reduction of the binding of the three ligands was 80% in the caudate and putamen. However, the decline in +MP pB in the ventral striatum (-75%) exceeded the declines of +DTBZ pB and FDOPA k(3)(S) in that region (-65%), suggesting that compensatory down-modulation of uptake sites may occur in the striatal regions with the least dopamine depletion. Binding of all three ligands was reduced by 50% in the anterior cingulate cortex and in the thalamus, suggesting toxicity of MPTP for extrastriatal catecholamine innervations. +DTBZ binding in the hypothalamus, presumably mainly in serotonin fibers, was unaffected by systemic MPTP treatment. Of the three tracers, +DTBZ was most sensitive for detecting MPTP-induced dopamine depletion in monkey striatum.
Doudet
Doris J
DJ
Department Medicine/Neurology and UBC/TRIUMFPET Program, University of British Columbia, Vancouver, Canada.
Rosa-Neto
Pedro
P
Munk
Ole L
OL
Ruth
Thomas J
TJ
Jivan
Salma
S
Cumming
Paul
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002421:Caudate Nucleus / Q000473:pathology; D003342:Corpus Striatum; D004292:Dominance, Cerebral / Q000502:physiology; D004296:Dopa Decarboxylase / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009412:Nerve Fibers / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018377:Neurotransmitter Agents / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis; D020734:Parkinsonian Disorders / Q000473:pathology*; D049268:Positron-Emission Tomography; D012016:Reference Values; D012701:Serotonin / Q000032:analysis; D013378:Substantia Nigra / Q000473:pathology; D013572:Synaptic Vesicles / Q000473:pathology
D018377:Neurotransmitter Agents; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004296:Dopa Decarboxylase; D004298:Dopamine; D009638:Norepinephrine