scholarly journals A Non-invasive Digital Biomarker for the Detection of Rest Disturbances in the SOD1G93A Mouse Model of ALS

2020 ◽  
Vol 14 ◽  
Author(s):  
Elisabetta Golini ◽  
Mara Rigamonti ◽  
Fabio Iannello ◽  
Carla De Rosa ◽  
Ferdinando Scavizzi ◽  
...  
Author(s):  
E. Golini ◽  
M. Rigamonti ◽  
F. Iannello ◽  
C. De Rosa ◽  
F. Scavizzi ◽  
...  

AbstractAmyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest.We used an automated home cage monitoring system (DVC®) to capture activity patterns that can potentially be associated with sleep and rest disturbances and thus to the progression of ALS in the SOD1G93A mouse model. DVC® enables non-intrusive 24/7 long term animal activity monitoring, which we assessed together with body weight decline and neuromuscular function deterioration measured by grid hanging and grip strength tests in male and female mice from 7 until 24 weeks of age.We show that as the ALS progresses over time in SOD1G93A mice, activity patterns during day time start becoming irregular, with frequent activity bouts that are neither observed in control mice nor in SOD1G93A at a younger age. The increasing irregularities of activity patterns during day time are quantitatively captured by designing a novel digital biomarker, referred to as Rest Disturbance Index (RDI). We show that RDI is a robust measure capable of detecting rest/sleep-related disturbances during the disease progression earlier than conventional methods, such as the grid hanging test. Moreover RDI highly correlates with grid hanging and body weight decline, especially in males.The non-intrusive long-term continuous monitoring of animal activity enabled by DVC® has been instrumental in discovering activity patterns potentially correlated with sleep and rest disturbances in the SOD1G93A mouse model of the ALS disease.


2013 ◽  
Vol 22 (9) ◽  
pp. 1783-1790 ◽  
Author(s):  
Ines Taes ◽  
Mieke Timmers ◽  
Nicole Hersmus ◽  
André Bento-Abreu ◽  
Ludo Van Den Bosch ◽  
...  

2019 ◽  
Author(s):  
Xueyuan Hu ◽  
Yonghui Yu ◽  
Junxia Feng ◽  
Mengjiao Fu ◽  
Lupeng Dai ◽  
...  

Abstract Background: Q fever is a worldwide zoonosis caused by Coxiella burnetii and mainly transmitted by aerosols. This study aims at establishing a systematic and efficient mouse model of acute Q fever via intratracheal (IT) inoculation of aerosolized C. burnetii. Methods: BALB/c mice were infected with C. burnetii via IT route using a non-invasive aerosol pulmonary delivery device to directly place the living C. burnetii organisms into their tracheas. The bacterial loads, pathological lesions, and serological responses were analyzed in mice, and compared with those of mice infected via intraperitoneal (IP) route. Results: As early as at day three post-infection (pi) with a low dose of C. burnetii (1×10⁴ per mouse), a large amount of C. burnetii organisms were determined in blood, lungs, hearts, livers, and spleens of the mice. The inflammatory infiltration was observed in hearts and lungs of mice. Compared with mice infected via IP route, the mice infected via IT route exhibited a higher level of bacterial loads and more severe pathological lesions in hearts and lungs at day 3 and day 7 pi. Conclusions: These data indicated that IT route is more efficient than IP route to cause acute C. burnetii infection in mice. Overall, we successfully established a mouse model of C. burnetii infection via IT route, which is useful for investigations of pathogenesis and immunity of acute C. burnetii infection as well as evaluation of therapeutic drugs and preventive vaccines of Q fever.


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