Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer's disease.
Transgenic mouse models of Alzheimer's disease (AD) have been recently advanced. Tg2576 mice have been shown to develop progressive beta-amyloid (Abeta) neuritic plaques and exhibit impairment of cognitive function. The aim of this study was a better characterization of different aspects of spatial memory performance of transgenic mice, observed at a time when levels of soluble Abeta are elevated and Abeta neuritc plaques start to appear. A general elevation of basal locomotory activity in the home cage was found in Tg2576 mice, which also exhibited an impairment of spontaneous alternation in the Y-maze test. Tg2576 mice were not flexible upon changes in the schedule and failed to codify spatially the testing environment. Consistently, a deficit of spatial memory was also observed when mice were assessed for levels of reactivity to spatial change in the modified open-field test with objects. Compared to controls, Tg2576 mice also exhibited an increased number of explorative approaches to the different objects, and failed to discriminate the displacement of the object. Consistently with the hypothesis of increased disinhibition, a differential behavioural response to the plus-maze paradigm was exhibited by Tg2576 mice. Results clearly indicate that Tg2576 mice are characterized by a number of specific behavioral cognitive alterations, compatible with Alzheimer's disease (AD), which make them a suitable animal model for testing of novel anti-AD drugs.
Ognibene
Elisa
E
Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
Middei
Silvia
S
Daniele
Stefania
S
Adriani
Walter
W
Ghirardi
Orlando
O
Caprioli
Antonio
A
Laviola
Giovanni
G
D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002940:Circadian Rhythm / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D007266:Inhibition, Psychological; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011187:Posture / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology*; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor