Environmental enrichment eliminates the anxiety phenotypes in a triple transgenic mouse model of Alzheimer’s disease
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Although the impacts of environmental enrichment (EE) in several genetic models of Alzheimer’s disease (AD) have been documented, the focus has remained predominantly on cognition. Few have investigated the expression of emotional phenotypes that mimic the notable affective features in AD. Here, we studied the interaction between EE and the coexpression of three genetic risk factors (mutations) for AD. In a longitudinal design, 3×Tg-AD mutants and wild type controls were compared at 6–7 months and subsequently at 12–13 months of age. Under standard housing, phenotypes of heightened anxiety levels were identified in the 3×Tg-AD mice in the elevated plus maze and open-field tests. Such trait differences between genotypes were substantially diminished under EE housing, which was attributable to the anxiolytic impact of EE on the mutant mice as much as the anxiogenic impact of EE on the wild type mice. In contrast, the phenotypes in learned fear were not significantly modified by EE in the tests of Pavlovian freezing and conditioned active avoidance conducted at either age. Rearing under EE thus has uncovered a novel distinction between innate and acquired expressions of fear response in the 3×Tg-AD mouse model that might be relevant to the mental health management of AD.
KeywordsAnimal models Anxiety Emotion
The present study was supported by the Swiss National Science Foundation (Grant No. NSF 3100A0-100309), ETH Zurich, and the National Centre for Competence in Research (NCCR): Neural Plasticity and Repair. Frank M. Laferla (University of California, Irvine, USA) kindly provided us with breeders of the 3×Tg-AD line for generating the experimental subjects used in this study. The authors also thank the ETH animal husbandry staff and Frank Bootz for his veterinary supervision.
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