Proteomic analysis of spinal cord of presymptomatic amyotrophic lateral sclerosis G93A SOD1 mouse

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.

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Longitudinal assessment of metal concentrations and copper isotope ratios in the G93A SOD1 mouse model of amyotrophic lateral sclerosis

Metallomics ◽

10.1039/c6mt00270f ◽

2017 ◽

Vol 9 (2) ◽

pp. 161-174 ◽

Cited By ~ 6

Author(s):

T. Gabriel Enge ◽

Heath Ecroyd ◽

Dianne F. Jolley ◽

Justin J. Yerbury ◽

Anthony Dosseto

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Isotope Ratios ◽

Longitudinal Assessment ◽

Copper Isotope ◽

Metal Concentrations ◽

G93a Sod1 Mouse ◽

Sod1 Mouse ◽

G93a Sod1 ◽

Lateral Sclerosis

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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

10.1101/2020.06.25.096552 ◽

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.

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