scholarly journals Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of amyotrophic lateral sclerosis

2020 ◽  
Vol 598 (19) ◽  
pp. 4385-4403
Author(s):  
Dennis B. Jensen ◽  
Marion Kadlecova ◽  
Ilary Allodi ◽  
Claire F. Meehan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
G93a Sod1 Mouse ◽  
Spinal Motoneurones ◽  
Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

On the Relation of Oxidative Stress to Neuroinflammation: Lessons Learned from the G93A-SOD1 Mouse Model of Amyotrophic Lateral Sclerosis

2006 ◽  
Vol 8 (11-12) ◽  
pp. 2075-2087 ◽  
Author(s):  
Kenneth Hensley ◽  
Molina Mhatre ◽  
Shenyun Mou ◽  
Quentin N. Pye ◽  
Charles Stewart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Lessons Learned ◽  
G93a Sod1 Mouse ◽  
Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

Metabolic progression markers of neurodegeneration in the transgenic G93A-SOD1 mouse model of amyotrophic lateral sclerosis

2007 ◽  
Vol 25 (6) ◽  
pp. 1669-1677 ◽  
Author(s):  
Heiko G. Niessen ◽  
Grazyna Debska-Vielhaber ◽  
Kerstin Sander ◽  
Frank Angenstein ◽  
Albert C. Ludolph ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Progression Markers ◽  
G93a Sod1 Mouse ◽  
Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

scholarly journals Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis

2018 ◽  
Vol 39 (7) ◽  
pp. 1283-1298 ◽  
Author(s):  
Hongxia Lei ◽  
Elisabeth Dirren ◽  
Carole Poitry-Yamate ◽  
Bernard L Schneider ◽  
Rolf Gruetter ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Mouse Model ◽  
Disease Progression ◽  
Resonance Spectroscopy ◽  
Neurochemical Profiles ◽  
G93a Sod1 Mouse ◽  
Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

In vivo 1H magnetic resonance spectroscopy (1H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (−19%) and glutamate (+8%) of brainstem, along with γ-amino-butyric acid (−30%), N-acetyl-aspartate (−5%) and ascorbate (+51%) of motor cortex. With disease progression towards the end-stage, increased numbers of metabolic changes of G93A-SOD1 mice were observed (e.g. glutamine levels increased in the brainstem (>+66%) and motor cortex (>+54%)). Through ALS disease progression, an overall increase of glutamine/glutamate in G93A-SOD1 mice was observed in the striatum ( p < 0.01) and even more so in two motor neuron enriched regions, the brainstem and motor cortex ( p < 0.0001). These 1H-MRS data underscore a pattern of neurochemical alterations that are specific to brain regions and to disease stages of the G93A-SOD1 mouse model. These neurochemical changes may contribute to early diagnosis and disease monitoring in ALS patients.

scholarly journals Increased axon initial segment length results in increased Na+ currents in spinal motoneurones at symptom onset in the G127X SOD1 mouse model of Amyotrophic Lateral Sclerosis

2020 ◽  
Author(s):  
H. S. Jørgensen ◽  
D.B. Jensen ◽  
K.P. Dimintiyanova ◽  
V.S. Bonnevie ◽  
A. Hedegaard ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Models ◽  
Symptom Onset ◽  
Repetitive Firing ◽  
Spinal Motoneurones ◽  
Axon Initial Segments ◽  
Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1 mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice.These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na+ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na+ channels occurring at symptom onset in this model.HighightsIn vivo electrophysiological recordings were made in symptomatic G127X SOD1 mice.There were no deficits in repetitive firing in motoneurones in G127X mice.Increased persistent inward currents were still present in the symptomatic mice.Results suggest increases in Na+ currents at axon initial segments (AISs).Immunohistochemistry showed that motoneurone AISs were longer and thinner.

scholarly journals Perturbations in intracellular Ca2+ handling in skeletal muscle in the G93A*SOD1 mouse model of amyotrophic lateral sclerosis

2014 ◽  
Vol 307 (11) ◽  
pp. C1031-C1038 ◽  
Author(s):  
Eva R. Chin ◽  
Dapeng Chen ◽  
Kostyantyn D. Bobyk ◽  
Davi A. G. Mázala
Keyword(s):  
Skeletal Muscle ◽  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Disease Progression ◽  
Skeletal Muscle Atrophy ◽  
Fura 2 ◽  
Intracellular Ca ◽  
G93a Sod1 Mouse ◽  
G93a Sod1 ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by skeletal muscle atrophy and weakness, ultimately leading to respiratory failure. The purpose of this study was to assess changes in skeletal muscle excitation-contraction (E-C) coupling and intracellular Ca2+ handling during disease progression in the G93A*SOD1 ALS transgenic (ALS Tg) mouse model. To assess E-C coupling, single muscle fibers were electrically stimulated (10–150 Hz), and intracellular free Ca2+ concentration was assessed using fura-2. There were no differences in peak fura-2 ratio at any stimulation frequency at 70 days (early presymptomatic). However, at 90 days (late presymptomatic) and 120–140 days (symptomatic), fura-2 ratio was increased at 10 Hz in ALS Tg compared with wild-type (WT) fibers (0.670 ± 0.02 vs. 0.585 ± 0.02 for 120–140 days; P < 0.05). There was also a significant increase in resting fura-2 ratio at 90 days (0.351 ± 0.008 vs. 0.390 ± 0.009 in WT vs. ALS Tg; P < 0.05) and 120–140 days (0.374 ± 0.001 vs. 0.415 ± 0.003 in WT vs. ALS Tg; P < 0.05). These increases in intracellular Ca2+ in ALS Tg muscle were associated with reductions in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase proteins SERCA1 (to 54% and 19% of WT) and SERCA2 (to 56% and 11% of WT) and parvalbumin (to 80 and 62% of WT) in gastrocnemius muscle at 90 and 120–140 days, respectively. There was no change in dihydropyridine receptor/l-type Ca2+ channel at any age. Overall, these data demonstrate minimal changes in electrically evoked Ca2+ transients but elevations in intracellular Ca2+ attributable to decreased Ca2+-clearance proteins. These data suggest that elevations in cellular Ca2+ could contribute to muscle weakness during disease progression in ALS mice.

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