Indexes for flotation and circling, two non-search behaviors in the water maze, sensitive to d-galactose-induced accelerated aging and Alzheimer's disease

Abstract

The study of behavioral and psychological symptoms of dementia (BPSD) has been largely neglected in most experimental research on Alzheimer's disease (AD) classically focused on cognitive symptoms. The aquatic environment of the Morris water maze (MWM) implies a stressful condition for mice leading to cognitive performances with presence of other behaviors related to emotionality. This can be critical in models such as the 3xTg-AD mice that exhibit a noticeable BPSD-like profile. The present work is aimed to provide a quantitative (number of episodes and duration) and qualitative (prevalence) analysis of flotation and circling, the most common 'non-searching behaviors' elicited in the MWM. We studied the expression of these behaviors in 6-month-old gold-standard wildtype C57BL/6 mice (genetic background) and 3xTg-AD mice (onset of disease) and when both genotypes were submitted to chronic d-galactose induced accelerated aging. Elicitation of floating and circling was recorded during three standard MWM paradigms: visual perceptual learning, place task for spatial reference memory and a final probe trial for short-term memory. In view of the results, we demonstrate that the index of 'flotation', characteristic of non-transgenic performance, is sensitive (reduction) to accelerated aging and AD. Conversely, circling behavior, characteristic of 3xTg-AD mice, can be an additional tool for evaluating BPSD-like symptoms in AD-models while its index unveils bizarre behavior induced by d-galactose induced aging. These results can be useful in relation to preventive and/or therapeutical interventions targeting AD but they may also be suitable in the evaluation of the potential risk factors in animals with normal aging.

Keywords: 3xTg-AD mice; Accelerated aging; Aging; Alzheimer; BPSD; Bizarre; Circling; Flotation; Neuropsychiatric symptoms; d-Galactose.