Affiliations: [a] School of Psychology, Queen's University, Belfast, UK | [b] Immunodiagnostic Branch, Agri-food and Biosciences Institute, Belfast, UK | [c] Senexis Limited, Babraham Research Campus, Cambridge, UK | [d] School of Psychology, University of Ulster, Coleraine, UK
Correspondence:
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Correspondence to: Eugene O'Hare, School of Psychology, Queen's University, Belfast BT7 1NN, UK. Tel.: +44 2890 9754445; Fax: +44 2890 975486; E-mail: e.ohare@qub.ac.uk.
Abstract: The current study examined behavioral and histological effects of amyloid-β (Aβ) protein precursor (AβPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg− offspring. Tg+ rats and Tg− littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg+ rats and Tg− littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg+ rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed-consecutive number schedule at 3 months old, Tg− littermates demonstrated a longer latency to learning the response rule than Tg+ rats; while this might seem paradoxical, it is consistent with the role of overexpression of AβPP in learning. Histological analyses revealed activated astrocytes in brains of Tg+ rats but not Tg− littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg+ rats but not Tg− littermates. Quantification of Aβ load in the brain at 22 months indicated high levels of Aβ38, Aβ40, and Aβ42 in the Tg+ rats. These data suggest this model might provide a valuable resource for AD research.
Keywords: Amyloid-β protein precursor, animal model, behavior, histology, transgenic rat
