Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/ijms232213671
Keywords
Alzheimer's disease; animal model; sex differences; rehabilitation; exercise; physical activity; circadian rhythms
Funding
- European Union [737390]
- ArrestAD H2020 [Fet-OPEN-1-2016-2017-737390]
- [2017-SGR-1468]
- [UAB-GE-260408]
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The study showed that mice with exercise training exhibited higher levels of horizontal exploration in the open field test. There were sex-dependent differences in voluntary wheel running activity, with high-NIBI males running less than high-NIBI females. This may be influenced by NPS-like symptoms.
Alzheimer's disease (AD) patients suffer from circadian rhythm alterations affecting their daily physical activity patterns with less willingness to perform a voluntary exercise. In preclinical studies, there is no clarity on whether animal models of AD can replicate these impairments. Here, we provide a proof of concept of the performance and behavioral effects of four weeks of voluntary wheel running (VWR) in a group of 14-month-old male and female 3xTg-AD mice at advanced stages of AD and the daily variance (behavioral circadian rhythmicity) of VWR associated with sex and their neuropsychiatric-like phenotype. Higher levels of horizontal exploration in the open field (OF) test were found in mice submitted to exercise. A linear mixed effect model showed significant sex-dependent differences in the VWR activity performed on the first night of follow-up, with high-NIBI males running less than high-NIBI females. Thus, an influence of NPS-like symptoms on the circadian patterns of VWR may account for such differences. In addition, males remained more active than females during diurnal periods. We hypothesize that this increment in energy expenditure during resting periods may be related to hyperactive behavior, similar to that observed in humans' exacerbated agitation or sundowning behavior. These findings support the usage of the 3xTg-AD mouse as a reliable model for studying circadian rhythm alterations in AD and, at the translational level, the importance of tailored and individualized physical activity programs in clinical settings.
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