ArticleThe Journal of physiology2013
Selective mitochondrial Ca2+ uptake deficit in disease endstage vulnerable motoneurons of the SOD1G93A mouse model of amyotrophic lateral sclerosis.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Elucidating the Role of Cerebellar Synaptic Dysfunction in C9orf72-ALS/FTD - a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2022Pooled it
- Oxidative stress and inflammation in neurodegenerative disorders.Archives of toxicology · 2026Review
- Intranasal Dantrolene Nanoparticles for Treatment of Amyotrophic Lateral Sclerosis as a Disease-Modifying Drug.bioRxiv : the preprint server for biology · 2025Article
- Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.npj metabolic health and disease · 2025Review
- VEGF expression disparities in brainstem motor neurons of the SOD1Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Spinal Cord Injury Model Mitochondria Connect Altered Function with Defects of Mitochondrion Morphology: an Ultrastructural Study.Molecular neurobiology · 2024Article
- Targeting mitochondrial CaThe Journal of physiology · 2024Review
- Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.iScience · 2024Article
- Article
- Mitochondrial calcium cycling in neuronal function and neurodegeneration.Frontiers in cell and developmental biology · 2023Review
- Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.Frontiers in cell and developmental biology · 2023Review
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- SOD1 in ALS: Taking Stock in Pathogenic Mechanisms and the Role of Glial and Muscle Cells.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- In vivo brain imaging of mitochondrial CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- Dysfunction of Mitochondrial CaFrontiers in cell and developmental biology · 2020Review
- Chinese Herbal Medicine Interventions in Neurological Disorder Therapeutics by Regulating Glutamate Signaling.Current neuropharmacology · 2020Review
- Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology.Science translational medicine · 2019Article
- Membralin deficiency dysregulates astrocytic glutamate homeostasis leading to ALS-like impairment.The Journal of clinical investigation · 2019Article
- Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function.Disease models & mechanisms · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that targets some somatic motoneuron populations, while others, e.g. those of the oculomotor system, are spared. The pathophysiological basis of this pattern of differential vulnerability, which is preserved in a transgenic mouse model of amyotrophic lateral sclerosis (SOD1(G93A)), and the mechanism of neurodegeneration in general are unknown. Hyperexcitability and calcium dysregulation have been proposed by others on the basis of data from juvenile mice that are, however, asymptomatic. No studies have been done with symptomatic mice following disease progression to the disease endstage. Here, we developed a new brainstem slice preparation for whole-cell patch-clamp recordings and single cell fura-2 calcium imaging to study motoneurons in adult wild-type and SOD1(G93A) mice up to disease endstage. We analysed disease-stage-dependent electrophysiological properties and intracellular Ca(2+) handling of vulnerable hypoglossal motoneurons in comparison to resistant oculomotor neurons. Thereby, we identified a transient hyperexcitability in presymptomatic but not in endstage vulnerable motoneurons. Additionally, we revealed a remodelling of intracellular Ca(2+) clearance within vulnerable but not resistant motoneurons at disease endstage characterised by a reduction of uniporter-dependent mitochondrial Ca(2+) uptake and enhanced Ca(2+) extrusion across the plasma membrane. Our study challenged the notion that hyperexcitability is a direct cause of neurodegeneration in SOD1(G93A) mice, but molecularly identified a Ca(2+) clearance deficit in motoneurons and an adaptive Ca(2+) handling strategy that might be targeted by future therapeutic strategies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.