Thigmotaxis Helps Differentiate Normal and Pathological Ageing Processes in a Mouse model of Alzheimer’s Disease ^†

Abstract

A decline in learning and remembering a spatial route often accompanies the normal ageing process. Impairments in spatial orientation manifest from the early stages of disabling cognitive diseases such as Alzheimer’s Disease (AD). In the preclinical field, detecting behavioural signs that help differentiate both entities improve understanding of the AD instauration process and promotes advances in novel treatments to ameliorate its impact. Here, the performance of 3xTg-AD mice of both sexes and their non-transgenic (NTg) (C57BL/6J) counterpart was evaluated at two time points (12 and 16-months of age) in the Morris water maze test, using a modified 5-day protocol for the assessment of cognitive and non-cognitive symptoms of dementia, followed by a multiple swim pattern identification within a single trial in the test. In the CUE stage, when a visible flag was available, the classical parameter of mean distance travelled until finding the platform showed that all animals learned the basic principles of the test more rapidly with a second experience (at 16 months of age). After switching the platform location in the Place task (PT) stage, mild variations in reference memory were detected along days at 12 months but not at 16 months of age. Later, in the removal (RMV) stage, where no platform was available, the 16-month-old 3xTg-AD male mice showed better results in short-term memory performance. However, when the swim pattern was visually analysed (qualitative analysis), persistence in Thigmotaxis episodes, a non-hippocampus-associated search strategy, was found in the pathological AD-like model but not in the NTg group, pointing out this pattern as a valuable differentiating trait. Finally, the multiple strategies approach seems valuable for differentiating both mice strains, despite a similar performance when quantitative parameters were analysed.