Abstract
The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer’s disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex- and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice.
Highlights
The behavioral and psychological symptoms associated with dementia (BPSD), including neuropsychiatric symptoms (NPS) such as anxiety and phobias, paranoia and delusion, hallucinations, stereotypes, and other disturbances, are comorbidities manifested in 50–90% of people with Alzheimer’s disease (AD) [1]
In the corner test (Figure 2), all the variables were sensitive to the aging factor, as the longitudinal analysis showed the reduction of the number of crossings (A, F(1,42) = 80.104; p < 0.001), the number of rearings (A, F(1,42) = 24.564; p < 0.001), the crossings/rearings ratio (A, F(1,42) = 23.903; p < 0.001), and, the enhancement of the latency of rearing (A, F(1,42) = 18.085; p < 0.001)
A reduction with aging in the ratio of crossings/rearings was presented in NTg-females (p = 0.001), AD-males (p = 0.021) and WT-males (p = 0.001)
Summary
The behavioral and psychological symptoms associated with dementia (BPSD), including neuropsychiatric symptoms (NPS) such as anxiety and phobias, paranoia and delusion, hallucinations, stereotypes, and other disturbances, are comorbidities manifested in 50–90% of people with Alzheimer’s disease (AD) [1] These non-cognitive problems affect their quality of life [2], are an important source of distress for patients and caregivers [3], and frequently lead to premature institutionalization [4]. The modeling of BPSD/NPS in basic and preclinical research of AD under the sex perspective is needed to develop better pharmacological and non-pharmacological preventive/therapeutical interventions that could be effectively translated into clinical scenarios In this context, natural species-typical behaviors representing active interaction with the environment are excellent ethological scenes to reflect the interplay of cognitive
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