Translational Research on Amyotrophic Lateral Sclerosis (ALS): The Preclinical SOD1 Mouse Model

Mina, Maria; Konsolaki, Eleni; Zagoraiou, Laskaro

doi:10.21767/2573-5349.100022

Cited by 4 publications

(2 citation statements)

References 109 publications

(124 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is therefore crucial to provide evidence of this early symptom and to propose a suitable tool to investigate circadian and sleep related disruption in a classical mouse model of ALS as the SOD1G93A transgenic strain ( Gurney et al, 1994 ). The SOD1G93A mouse model we used expresses multiple copies of the human mutated form of the SOD1 gene (on a C57BL/6J background) and it recapitulates the progressive symptomatology of the disease starting around 14–16 weeks of age: muscle weakness, tremors, body weight loss, limb paralysis, respiratory failure and death around 160–170 days or 24–25 weeks of age and it also presents ALS characteristic neurobiological substrates (cortical and spinal cord motor neuron degeneration, gliosis, neuroinflammation) ( Leitner et al, 2009 ; Mina et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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

Golini

Rigamonti²,

Iannello³

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Amyotrophic 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 irregular 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 start becoming irregular, especially during day time, with frequent activity bouts that are neither observed in control mice nor in SOD1G93A at a younger age. The increasing irregularities of activity pattern are quantitatively captured by designing a novel digital biomarker, referred to as Regularity Disruption Index (RDI). We show that RDI is a robust measure capable of detecting home cage activity patterns that could be related to rest/sleep-related disturbances during the disease progression. Moreover, the RDI rise during the early symptomatic stage parallels grid hanging and body weight decline. The non-intrusive long-term continuous monitoring of animal activity enabled by DVC ® has been instrumental in discovering novel activity patterns potentially correlated, once validated, with sleep and rest disturbances in the SOD1G93A mouse model of the ALS disease.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Golini

Rigamonti²,

Iannello³

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…It is therefore crucial to provide evidence of this early symptom and to propose a suitable tool to investigate circadian and sleep related disruption in a classical mouse model of ALS as the SOD1G93A transgenic strain [9]. The SOD1G93A mouse model we used expresses multiple copies of the human mutated form of the SOD1 gene (on a C57BL/6J background) and it recapitulates the progressive symptomatology of the disease starting around 14-16 weeks of age: muscle weakness, tremors, body weight loss, limb paralysis, respiratory failure and death around 160-170 days or 24-25 weeks of age and it also presents ALS characteristic neurobiological substrates (cortical and spinal cord motor neuron degeneration, gliosis, neuroinflammation) [10,11].…”

Section: Introductionmentioning

confidence: 99%

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

Golini

Rigamonti²,

Iannello³

et al. 2019

Preprint

View full text Add to dashboard Cite

Amyotrophic 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/sleeprelated 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.

show abstract

Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra‐high field MRI and diffusion tensor metrics

Gatto

Weissmann

Amin

et al. 2020

Anim Models and Exp Med

View full text Add to dashboard Cite

ObjectiveCell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis (ALS). In this work, we propose the use of diffusion tensor imaging (DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS.MethodsUltra‐high field MRI and DTI data at 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A‐SOD1) mice.ResultsChanges in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (CL, CP, and CS, respectively) of the diffusion eigenvalues were measured in white matter (WM) and gray matter (GM) areas associated with early axonal degenerative processes (in both the brain and the spinal cord). Specifically, in WM structures (corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, CL, and CP values decreased, whereas CS values increased. In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and CP decreased, whereas the CL and CS values were unchanged or slightly smaller. Histological studies of a fluorescent mice model (YFP, G93A‐SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI.ConclusionsChanges in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of CL, CP, and CS as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.

show abstract

Translational Research on Amyotrophic Lateral Sclerosis (ALS): The Preclinical SOD1 Mouse Model

Cited by 4 publications

References 109 publications

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

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

A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra‐high field MRI and diffusion tensor metrics

Contact Info

Product

Resources

About