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Titolo:
Brain energy metabolism in Alzheimer's disease: Tc-99m-HMPAO SPECT imagingduring verbal fluency and role of astrocytes in the cellular mechanism of Tc-99m-HMPAO retention
Autore:
Slosman, DO; Ludwig, C; Zerarka, S; Pellerin, L; Chicherio, C; de Ribaupierre, A; Annoni, JM; Bouras, C; Herrmann, F; Michel, JP; Giacobini, E; Magistretti, PJ;
Indirizzi:
Univ Lausanne, Fac Med, Inst Physiol, CH-1005 Lausanne, Switzerland Univ Lausanne Lausanne Switzerland CH-1005 CH-1005 Lausanne, Switzerland Univ Hosp Geneva, Div Nucl Med, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland , Div Nucl Med, Geneva, Switzerland Univ Hosp Geneva, Dept Clin Neurosci & Dermatol, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland sci & Dermatol, Geneva, Switzerland Univ Hosp Geneva, Dept Geriatr, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland , Dept Geriatr, Geneva, Switzerland Univ Hosp Geneva, Dept Psychiat, Geneva, Switzerland Univ Hosp Geneva Geneva Switzerland Dept Psychiat, Geneva, Switzerland Univ Geneva, Fac Psychol & Educ Sci, Geneva, Switzerland Univ Geneva Geneva Switzerland Psychol & Educ Sci, Geneva, Switzerland
Titolo Testata:
BRAIN RESEARCH REVIEWS
fascicolo: 2-3, volume: 36, anno: 2001,
pagine: 230 - 240
SICI:
0165-0173(200110)36:2-3<230:BEMIAD>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; PROPYLENEAMINE OXIME; FDG-PET; GLUTATHIONE; ACTIVATION; MEMORY; CULTURES; TECHNETIUM-99M-MESO-HMPAO; ABNORMALITIES; HYPERFIXATION;
Keywords:
single photon emission computed tomography (SPECT); functional imaging; astrocytes; brain energy metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Magistretti, PJ Univ Lausanne, Fac Med, Inst Physiol, 7 Rue Bugnon, CH-1005 Lausanne, Switzerland Univ Lausanne 7 Rue Bugnon Lausanne Switzerland CH-1005 d
Citazione:
D.O. Slosman et al., "Brain energy metabolism in Alzheimer's disease: Tc-99m-HMPAO SPECT imagingduring verbal fluency and role of astrocytes in the cellular mechanism of Tc-99m-HMPAO retention", BRAIN RES R, 36(2-3), 2001, pp. 230-240

Abstract

The central hypothesis of the study which has been carried out as part of the NRP38 program, is that perturbations of brain energy metabolism are critically involved in the neuro degeneration occurring in Alzheimer's disease(AD) and that they may correlate with early cognitive dysfunctioning. In the present multidisciplinary study we set out to monitor brain energy metabolism using FDG-PET and HMPAO-SPECT imaging in a cohort of individuals over65 years of age, drawn from the general population. HMPAO-SPECT imaging, which is a simpler and more widely accessible imaging procedure than FDG-PET, was performed under basal conditions and during the performance of a cognitive task (verbal fluency test). Three groups were studied. Two groups (groups I and II) included individuals age 65 or more, with no cognitive impairment and carrying an APOE4 positive or APOE4 negative phenotype, respectively; a third group (group III) included patients with clinical signs of AD. Each subject entering the study under-went an FDG-PET, an HMPAO-SPECT and an extensive battery of neuropsychological tests which assess various aspects of cognitive functioning, with a strong emphasis on working memory, divided attention and executive functions. A total of 101 participants were submitted to brain imaging and neuropsychological testing. Among these, 60 participants received the same set of imaging and neuropsychological tasks 24-36 months after the first set (phase II). In this article, we present a preliminary analysis performed on ten subjects from groups I and Il and nine subjects from group III: activation (verbal fluency task) induced a specificpattern of increase in HMPAO retention (including BA 9/10, BA 18 bilaterally and right BA 17). In contrast to controls, in nine AD subjects no significant differences in HMPAO retention were observed when comparing activation and basal conditions. The cellular and molecular mechanisms that underliethe retention of HMPAO, the tracer used for single photon emission computed tomography (SPECT) imaging has been studied in vitro in purified preparations of neurons and astrocytes with the aim of investigating the contribution of different cell types to hexamethyl-propylencamineoxime labeled with technetium-99m (Tc-99m-HMPAO) retention in vitro. Results show that Tc-99m-HMPAO retention predominates in astrocytes over neurons by a factor of similar to2.5. Diethyl maleate, ethacrynic acid and buthionine sulfoximine, three agents which significantly reduce glutathione levels, also decreased Tc-99m-HMPAO retention in both astrocytes and in neurons. Decrease did not always correlate with glutathione levels however, thus suggesting that other factors could be involved. The data presented indicate that astrocytes might constitute a prominent site of Tc-99m-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, they also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in Tc-99m-HMPAO retention in the brain as observed by SPECT in certain pathologies (including Alzheimer's disease). In particular, these observations suggest a key role of astrocytes in the signal detected with the imaging procedure. which is altered in the Alzheimer's cohort subjected to the verbal fluency activation task. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:21:25