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IC‐P‐007: Memory loss in young APPswe/PS1dE9 mice and associated changes in brain metabolism analyzed using a 3‐D voxel‐based approach
Author(s) -
Hérard AnneSophie,
Delzescaux Thierry,
Cornet Sylvie,
Lebenberg Jessica,
Chabrier PierreEtienne,
Hantraye Philippe,
Dhenain Marc
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.027
Subject(s) - genetically modified mouse , neuroscience , pathology , medicine , chemistry , nuclear medicine , psychology , transgene , biochemistry , gene
[gamma] (PPAR[gamma]) agonist, has an anti-inflammatory effect in the brain, decreasing interleukin-1[beta] concentrations in hippocampus and restoring the age-related deficit in long-term potentiation. It also attenuates learning and memory deficits in a mouse model of Alzheimer’s disease. Evidence suggests that activation of microglia and astrocytes contribute to agerelated neuroinflammatory changes. In this study, relaxometry measurements were assessed in hippocampus of young and aged rats because there have been recent reports in the literature linking spin-lattice (T1) and spinspin (T2) relaxation times to astrocytic activation and microglial activation respectively. Methods: Male Wistar rats aged 3 and 18 months (n 1⁄4 5-6 per group) were treated either with 3 mg/day rosiglitazone maleate or with vehicle only for 56 days and MR images obtained under anesthesia using a 7-Tesla MRI scanner (Bruker) with slices selected to give optimal regions of interest in dorsal hippocampus (Fig. 1). Images were acquired using rapid acquisition with relaxation enhancement (RARE) and echotrain multi-slice-multi-echo (MSME) sequences, from which T1 and T2 maps were generated, respectively; and a fast imaging with steady-state precession (FISP) protocol, from which both T1 and T2 maps were generated. Data from manually-selected regions of interest were analyzed using software scripts in IDL language (ITTVIS). Oneor two-way analyses of variance (ANOVA) with Fischer’s post-test were used to statistically assess the data. Tissue from the animals was examined for markers of astrogliosis and microglial activation. Results: T1 in hippocampus and cortex (p < 0.01, Fig. 2) were significantly increased with age whilst T2 in hippocampus (p < 0.05) and cortex (p < 0.01, Fig. 3) were significantly decreased with age. Treatment with rosiglitazone significantly attenuated the age-related T1 increase in both regions (p < 0.05, Fig. 2) and it increased T2 relaxation time in hippocampus of aged, but not young rats (p < 0.05, Fig. 3). Conclusions: The data demonstrate an age-related increase in T1 in hippocampus and cortex, which is attenuated by rosiglitazone; this correlates with astrocytosis (Fig. 4). We also show a decrease in T2 relaxation time in hippocampus and cortex, which correlates with an increase in microglial activation (Fig. 5), and report that rosiglitazone-treatment of aged rats increases hippocampal T2. IC-P-007 MEMORY LOSS IN YOUNG APPSWE/PS1DE9 MICE AND ASSOCIATED CHANGES IN BRAIN METABOLISM ANALYZED USING A 3-D VOXELBASED APPROACH Anne-Sophie Hérard, Thierry Delzescaux, Sylvie Cornet, Jessica Lebenberg, Pierre-Etienne Chabrier, Philippe Hantraye, Marc Dhenain, CEA-MIRCen-CNRS URA 2210, Fontenay-Aux-Roses, France; SCRAS-IHB, Les Ulis, France. Contact e-mail: anne-sophie. herard@cea.fr