RESUMO
OBJECTIVE: The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET). METHODS: We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K (1), k (2), k (3), k (4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k (3) to k (4) was computed as the binding potential (BP), which is linearly related to the density of sigma(1) receptors. Unpaired t tests were used to compare K (1) and BP in patients with AD and normal subjects. RESULTS: As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K (1) was significantly lower in the parietal lobe. CONCLUSIONS: [(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma(1) receptors is reduced in early AD.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Receptores sigma/análise , Idoso , Química Encefálica , Radioisótopos de Carbono/farmacocinética , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Humanos , Masculino , Piperazinas/farmacocinética , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Receptores sigma/química , Tálamo/diagnóstico por imagem , Tálamo/patologia , Distribuição TecidualRESUMO
Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.