Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with 18F-MNI-659 and 11C-raclopride with correction for partial volume effect.
Neuroimage
; 152: 330-339, 2017 05 15.
Article
en En
| MEDLINE
| ID: mdl-28254508
ABSTRACT
Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington´s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D2/3 receptors (D2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age 44±11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand 18F-MNI-659 and D2/3 R radioligand 11C-raclopride were used. The outcome measure was the binding potential (BPND) estimated with the two-tissue compartment model (18F-MNI-659) and the simplified reference tissue model (11C-raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in the striatum. Moreover as result of the analysis, in the striatum for both the molecular targets, we observed a gender effect with higher BPND the female group.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ganglios Basales
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Envejecimiento
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Receptores de Dopamina D2
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Hidrolasas Diéster Fosfóricas
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Receptores de Dopamina D3
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuroimage
Asunto de la revista:
DIAGNOSTICO POR IMAGEM
Año:
2017
Tipo del documento:
Article