Long-term monitoring reveals immobility-defined sleep fragmentation and behavioural alterations in collagen-induced arthritis mouse model of both sexes.

Rheumatoid arthritis is an autoimmune disease that impairs musculoskeletal function and overall well-being, often disrupting sleep and worsening cognitive and behavioural outcomes. While animal models of collagen-induced arthritis (CIA) are widely used, sleep behaviour in arthritic mice remains poorly studied. This study aimed to evaluate immobility-defined sleep behaviour in the CIA mouse model using continuous, non-invasive, long-term monitoring (LTM). CIA was induced in 12-month-old DBA/1J mice (females: n = 13; males: n = 17) using type II collagen and complete Freund's adjuvant. On day 63 post-induction, immobility-defined sleep behaviour was recorded over 12hours (6-hour rest and 6-hour active phase) in PhenoTyper cages. Behavioural tests included open field, novel object recognition, reciprocal interaction, and nesting. During the rest phase of LTM, CIA mice showed 50% less immobility-defined sleep time, shorter sleep bouts, and more frequent sleep interruptions, while in the active phase of LTM, CIA mice showed 50% reduced locomotor activity as well. They also showed worse short-term memory, 50% higher anxiety-like behaviour, 5-fold more self-grooming, and up to 80% less exploration than controls. CIA mice showed 50% less social interactions than controls, while CIA females spent more time in feeding and drinking zones. In CIA mice, more frequent interruptions of immobility-defined sleep were associated with higher arthritis scores, while associations with reduced nest building and rearing, elevated self-grooming, and larger hind-paw volume were moderate, but did not survive multiple testing corrections. Overall, CIA mice showed altered immobility-defined sleep continuity alongside broader functional deficits, some of which were sex-specific. These findings support LTM as a complementary approach to characterising sleep-related and behavioural alterations in experimental arthritis, and open new avenues for exploring the role of sleep in the overall well-being of patients with rheumatoid arthritis.