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Behav Brain Res. 2009 Jul 19;201(1):147-57. doi: 10.1016/j.bbr.2009.02.005. Epub 2009 Feb 13.

Characterization of cognition alteration across the course of the disease in APP751SL mice with parallel estimation of cerebral Abeta deposition.

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Centre for Integrative and Cognitive Neuroscience, University of Bordeaux, CNRS UMR 5228, Talence, France.


Current transgenic mouse models of Alzheimer disease constitute a relevant tool to examine the relationships between neuropathological lesions, neurodegeneration and clinical syndromes. Nevertheless, addressing the relation between Abeta deposition and cognition deterioration requires careful adjustment for age to decipher underlying mechanisms of impairments and identify potential therapeutic targets. In the present work we have carried out a detailed behavioral analysis of the APP(751SL) transgenic mouse model testing 6 age-points (from 2 to 19-20 months) and estimating in parallel the cerebral Abeta deposition. The immunohistochemistry study indicated a fast progression of Abeta(17-24) staining in several brain structures that reached for most of them, a maximal level at 7-8 months of age. Behavioral experiments showed that APP(751SL) mice displayed alterations in some general functions (muscular strength, motor activity) whereas other functions are preserved (anxiety, exploration). Acquisition and extinction of an appetitive operant conditioning were used to assess early learning deficits. Hippocampal but not dorso-lateral striatal lesion was shown to delay extinction. Although some learning deficits were detected at 5-6 months in the acquisition of the operant conditioning task, more robust impairments in extinction were observed in 7-8-month-old mice. Indeed, spatial memory deficit was associated to a selective hippocampal CA1 impairment of learning-induced Zif268 activation. Because this mouse model displayed gradual memory deficits it gives the opportunity to investigate the temporal progression of molecular and cellular mechanisms that induce cognitive decline.

[Indexed for MEDLINE]

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