Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography

Citation
N. Omata et al., Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography, DEMENT G C, 12(2), 2001, pp. 78-84
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS
ISSN journal
1420-8008 → ACNP
Volume
12
Issue
2
Year of publication
2001
Pages
78 - 84
Database
ISI
SICI code
1420-8008(200103/04)12:2<78:ACIEPI>2.0.ZU;2-V
Abstract
To investigate age-related changes in cerebral energy production, we compar ed senescence-accelerated prone mice (SAMP8) as an animal model of accelera ted aging and senescence-accelerated resistant mice (SAMR1) as a control. C onsidering that the cerebral glucose metabolic rate (CMRglc) at the time of O-2 deprivation and 2,4-dinitrophenol (DNP) loading would reflect anaerobi c glycolytic capacity and mitochondrial function, respectively, we investig ated dynamic changes in CMRglc before and after loading with these perturba tions. Fresh brain slices were incubated with [F-18]2-fluoro-2-deoxy-D-gluc ose ([F-18]FDG) in oxygenated Krebs-Ringer solution at 36 degreesC, and ser ial two-dimensional time-resolved images of [F-18]FDG uptake in these slice s were obtained on the imaging plates. The fractional Fate constant (=k(3)* ) of [F-18]FDG proportional to the CMRglc was evaluated by applying the Gje dde-Patlak graphical method to the image data. The k(3)* value before the h ypoxic perturbation in all of the brain sites analyzed was higher in SAMP8 than SAMR1 in both the 2- and 10-month-old groups. With O-2 deprivation, k( 3)* values were higher without site specificity in the 2-month-old SAMP8 th an in 2-month-old SAMR1, whereas in 10-month-old mice, there was no signifi cant difference between the two groups. In contrast, with DNP loading, whil e no significant difference was noted between 2-month-old SAMP8 and 2-month -old SAMR1, in 10-month-old mice, the SAMP8 group showed lower values in ce rtain regions than SAMR1 mice. These results suggest that in the brain tiss ue of SAMP8, a marked transient enhancement of anaerobic glycolytic capacit y in the 2-month-olds and a decrease in mitochondrial function in the subse quent period occur, as a result of which glucose metabolism appears to be e nhanced in both the 2- and 10-month-old groups compared to SAMR1 mice. Copy right (C) 2001 S. Karger AG, Basel.