Home cage detection of sleep disturbances in a mouse model of ALS

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects central and peripheral nervous systems, leading to the degeneration of motor neurons, and resulting in muscle atrophy, paralysis and death. Sleep disturbances are common in patients with ALS and other neurodegenerative diseases, causing even further deteriorated quality of life. We used an automated home cage monitoring system (DVC®) to capture irregular activity patterns potentially associated with rest disturbances and to disease progression in the SOD1G93A mouse model. DVC® enables non-intrusive 24/7 long term activity monitoring, assessed together with body weight decline and neuromuscular function deterioration (grid hanging and grip strength tests) in males and females from age 7 until 24 weeks. Activity of SOD1G93A mice start becoming irregular at 14 weeks, especially during day time, with frequent bouts not observed in controls or younger SOD1G93A mice. We created the Regularity Disruption Index (RDI) to quantify these irregularities of activity. RDI is a robust measure for detecting home cage activity related to rest/sleep disturbances. Its rise during early symptomatic stages parallels neuromuscular and weight decline. The non-intrusive long-term continuous monitoring of activity can been instrumental in discovering novel activity patterns potentially correlated with sleep disturbances in models of neurodegenerative disorders.