Astrocytes carrying the superoxide dismutase 1 (SOD1 G93A ) mutation induce wild-type motor neuron degeneration in vivo
Open accessAbstract
Recent studies highlight astrocytes as key drivers of motor neuron (MN) degeneration and disease propagation in mutant human superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis. However, in vivo analysis of specific astrocytic influence in amyotrophic lateral sclerosis has proven difficult because mSOD1 is ubiquitously expressed throughout the CNS of rodent models studied. Here, we transplanted SOD1 G93A glial-restricted precursor cells—glial progenitors capable of differentiating into astrocytes—into the cervical spinal cord of WT rats to reveal how mutant astrocytes influence WT MNs and other cells types (microglia and astrocytes) in an in vivo setting. Transplanted SOD1 G93A glial-restricted precursor cells survived and differentiated efficiently into astrocytes. Graft-derived SOD1 G93A astrocytes induced host MN ubiquitination and death, forelimb motor and respiratory dysfunction, reactive astrocytosis, and reduced GLT-1 transporter expression in WT animals. The SOD1 G93A astrocyte-induced MN death seemed in part mediated by host microglial activation. These findings show that mSOD1 astrocytes alone can induce WT MN death and associated pathological changes in vivo.
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Transplantation of SOD1G93A astrocytes into the spinal cords of wild-type mice induced motor neuron loss.
“transplantation of SOD1G93A astrocytes into the spinal cords of wild-type mice induced motor neuron loss [347].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [347]
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“Supporting the notion of non-cell autonomous contributions to disease, transplantation of SOD1 astrocytes into the spinal cords of wild-type mice induced motor neuron loss [347].”
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- Authors
- Papadeas, S. T., Kraig, S. E., O'Banion, C., Lepore, A. C., & Maragakis, N. J.
- Affiliations
- Johns Hopkins University (US)
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
- Corresponding author
- Maragakis, Nicholas J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-10-03
- Volume
- 108
- Issue
- 43
- Pages
- 17803-17808
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3203804
- OpenAlex
- W1990078383
- Cited by
- 213
- References
- 36
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 23 · 2022: 14 · 2021: 17 · 2020: 14 · 2019: 14 · 2018: 12 · 2017: 14 · 2016: 12 · 2015: 14 · 2014: 21 · 2013: 18 · 2012: 14
- FWCI
- 11.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- ALS Association
- Muscular Dystrophy Association
- Maryland Stem Cell Research Fund
- Robert Packard Center for ALS Research, Johns Hopkins University
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- amyotrophic lateral sclerosis, superoxide dismutase 1, SOD1 G93A mutation, astrocytes, motor neuron degeneration, cell transplantation, reactive astrogliosis, glutamate uptake, microglial activation, disease propagation, cervical spinal cord
- MeSH terms
- Superoxide Dismutase-1, Analysis of Variance, Animals, Astrocytes, Cell Differentiation, Humans, Nerve Degeneration, Neuroglia, Superoxide Dismutase, Cell Death, Point Mutation, Excitatory Amino Acid Transporter 2, Stem Cell Transplantation, Rats, Ubiquitination
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