Search Strategy Analysis of 5xFAD Alzheimer Mice in the Morris Water Maze Reveals Sex- and Age-Specific Spatial Navigation Deficits

• Published in: Biomedicines 2023-02, Vol.11 (2), p.599
• Main Authors: Sánchez, Carolina Quintanilla, Schmitt, Franziska W, Curdt, Nadine, Westhoff, Anna Celine, Bänfer, Irina Wanda Helene, Bayer, Thomas A, Bouter, Yvonne
• Format: Article
• Language: English
• Subjects: 5xFAD mice; Age; Alzheimer's disease; Alzheimer’s disease (AD); Animal cognition; Animal memory; cognitive impairments; mouse model; Mutation; Navigation behavior; navigation strategy; Neurodegenerative diseases; Physiological aspects; search strategy analysis; Short term memory; Spatial discrimination learning; Spatial memory; Swimming
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11020599

Spatial disorientation and navigational impairments are not only some of the first memory deficits in Alzheimer's disease, but are also very disease-specific. In rodents, the Morris Water Maze is used to investigate spatial navigation and memory. Here, we examined the spatial memory in the commonly used 5xFAD Alzheimer mouse model in a sex- and age-dependent manner. Our findings show first spatial learning deficits in 7-month-old female 5xFAD and 12-month-old male 5xFAD mice, respectively. While the assessment of spatial working memory using escape latencies provides a global picture of memory performance, it does not explain how an animal solves a spatial task. Therefore, a detailed analysis of swimming strategies was performed to better understand the behavioral differences between 5xFAD and WT mice. 5xFAD mice used a qualitatively and quantitatively different search strategy pattern than wildtype animals that used more non-spatial strategies and showed allocentric-specific memory deficits. Furthermore, a detailed analysis of swimming strategies revealed allocentric memory deficits in the probe trial in female 3-month-old and male 7-month-old 5xFAD animals before the onset of severe reference memory deficits. Overall, we could demonstrate that spatial navigation deficits in 5xFAD mice are age- and sex-dependent, with female mice being more severely affected. In addition, the implementation of a search strategy classification system allowed an earlier detection of behavioral differences and therefore could be a powerful tool for preclinical drug testing in the 5xFAD model.