PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain.
Cereb Cortex
; 31(6): 2787-2798, 2021 05 10.
Article
em En
| MEDLINE
| ID: mdl-33442731
ABSTRACT
Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n = 4) and nonhuman primates (n = 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n = 10) scanned with the α4ß2* nicotinic ligand (-)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions, p = 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%, p < 0.0001; α4ß2*/nicotine scans, 67 ± 15% vs. 74 ± 16%, p = 0.0065), indicating higher striatal ACh concentration. Subject-level measures of these concentration differences were estimated, and whole-brain images of regional ACh concentration gradients were generated. These results constitute the first in vivo estimates of regional variation in ACh concentration in the living brain and offer a novel experimental method to assess potential ACh imbalances in clinical populations.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Acetilcolina
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Compostos Radiofarmacêuticos
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Tomografia por Emissão de Pósitrons
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cereb Cortex
Assunto da revista:
CEREBRO
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos