Age-dependent and -independent behavioral deficits in Tg2576 mice

被引:95
作者
Deacon, R. M. J. [1 ]
Cholerton, L. L. [1 ]
Talbot, K. [1 ]
Nair-Roberts, R. G. [1 ]
Sanderson, D. J. [1 ]
Romberg, C. [1 ]
Koros, E. [2 ]
Bornemann, K. D. [2 ]
Rawlins, J. N. P. [1 ]
机构
[1] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England
[2] Boehringer Ingelheim Pharma GmbH & Co KG, Dept CNS Res, Biberach, Germany
基金
英国惠康基金;
关键词
Tg2576; mice; Alzheimer's disease; mouse; learning; memory; paddling; Y-maze; amyloid; APPswe;
D O I
10.1016/j.bbr.2007.12.024
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
The Tg2576 mouse model of excessive cerebral P-amyloid deposition is now more than a decade old, yet consensus as to its exact characteristics and utility as a model of Alzheimer's disease is still lacking. Four different cohorts of control and Tg2576 mice, aged approximately 3, 9, 13 and 21 months, were therefore subjected to a battery of tests, principally to assess cognitive and species-typical behaviors. A novel test, the paddling Y-maze, demonstrated an age-dependent deficit in 10 and 14, but not 3 month Tg2576 mice, also in aged (21 month) control mice. However, in many other cognitive tests few Tg2576-related deficits could be shown. This frequently seemed attributable to poor performance of control mice. Tests of species-typical behaviors showed that Tg2576 mice had a deficit in burrowing behavior at all ages. An age-independent deficit was also seen in nest construction, but only when mice were group-housed; most individually housed mice in either group made reasonable nests. Overall, the results suggested that these Tg2576 mice are not a simple, suitable or reliable model for routine screening of treatments for Alzheimer's disease. However, this model might perform better behaviorally on a different genetic background. (c) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:126 / 138
页数:13
相关论文
共 51 条
[1]   Multi-metric behavioral comparison of APPsw and P30IL models for Alzheimer's Disease: linkage of poorer cognitive performance to tau pathology in forebrain [J].
Arendash, GW ;
Lewis, J ;
Leighty, RE ;
McGowan, E ;
Cracchiolo, JR ;
Hutton, M ;
Garcia, MF .
BRAIN RESEARCH, 2004, 1012 (1-2) :29-41
[2]   Mechanisms of memory loss in Aβ and tau mouse models [J].
Ashe, KH .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2005, 33 :591-594
[3]   Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice [J].
Chapman, PF ;
White, GL ;
Jones, MW ;
Cooper-Blacketer, D ;
Marshall, VJ ;
Irizarry, M ;
Younkin, L ;
Good, MA ;
Bliss, TVP ;
Hyman, BT ;
Younkin, SG ;
Hsiao, KK .
NATURE NEUROSCIENCE, 1999, 2 (03) :271-276
[4]   Genes, models and Alzheimer's disease [J].
Chapman, PF ;
Falinska, AM ;
Knevett, SG ;
Ramsay, MF .
TRENDS IN GENETICS, 2001, 17 (05) :254-261
[5]  
COMET C, 2001, BEHAV BRAIN RES, V124, P33
[6]   Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer's disease [J].
Corcoran, KA ;
Lu, Y ;
Turner, RS ;
Maren, S .
LEARNING & MEMORY, 2002, 9 (05) :243-252
[7]   Hippocampal lesions, species-typical behaviours and anxiety in mice [J].
Deacon, RMJ ;
Rawlins, JNP .
BEHAVIOURAL BRAIN RESEARCH, 2005, 156 (02) :241-249
[8]   Learning impairments of hippocampal-lesioned mice in a paddling pool [J].
Deacon, RMJ ;
Rawlins, JNP .
BEHAVIORAL NEUROSCIENCE, 2002, 116 (03) :472-478
[9]   Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery [J].
Deacon, RMJ ;
Bannerman, DM ;
Kirby, BP ;
Croucher, A ;
Rawlins, JNP .
BEHAVIOURAL BRAIN RESEARCH, 2002, 133 (01) :57-68
[10]   Hippocampal cytotoxic lesion effects on species-typical behaviours in mice [J].
Deacon, RMJ ;
Croucher, A ;
Rawlins, JNP .
BEHAVIOURAL BRAIN RESEARCH, 2002, 132 (02) :203-213