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

ORCID
0000-0002-0595-6162
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Sánchez, Carolina Quintanilla;
ORCID
0000-0002-6878-6084
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Schmitt, Franziska W.;
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Curdt, Nadine;
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Westhoff, Anna Celine;
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Bänfer, Irina Wanda Helene;
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Bayer, Thomas A.;
Affiliation
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center (UMG), Georg-August-University, 37075 Goettingen, Germany
Bouter, Yvonne

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.

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