Kyphosis and bizarre patterns impair spontaneous gait performance in end-of-life mice with Alzheimer's disease pathology while gait is preserved in normal aging

Abstract

The shorter life spans of mice provide an exceptional experimental gerontology scenario. We previously described increased bizarre (disruptive) behaviors in the 6-month-old 3xTg-AD mice model for Alzheimer's disease (AD), compared to C57BL/6J wildtype (NTg), when confronting new environments. In the present work, we evaluated spontaneous gait and exploratory activity at old age, using 16-month-old mice. Male sex was chosen since sex-dependent psychomotor effects of aging are stronger in NTg males than females and, at this age, male 3 × Tg-AD mice are close to an end-of-life status due to increased mortality rates. Mice's behavior was evaluated in a transparent test box during the neophobia response. Stretching, jumping, backward movements and bizarre circling were identified during the gait and exploratory activity. The results corroborate that in the face of novelty and recognition of places, old 3xTg-AD mice exhibit increased bizarre behaviors than mice with normal aging. Furthermore, bizarre circling and backward movements delayed the elicitation of locomotion and exploration, in an already frail scenario, as shown by highly prevalent kyphosis in both groups. Thus, the translational study of co-occurrence of psychomotor impairments and anxiety-like behaviors can be helpful for understanding and managing the progressive functional deterioration shown in aging, especially in AD.