Mutant SOD1G93A microglia are more neurotoxic relative to wild‐type microglia
Abstract
Recent studies suggest that microglia over‐expressing mutant human superoxide dismutase (mSOD1 G93A) may contribute to motoneuron death in a transgenic mouse model of familial amyotrophic lateral sclerosis. To further assess the relative neurotoxicity of wild‐type microglia, mSOD1 G93A microglia, and microglia over‐expressing wild‐type human SOD1, we used primary cultures of microglia and motoneurons in the presence and absence of lipopolysaccharide stimulation. Following activation with lipopolysaccharide, mSOD1 G93A microglia released more nitric oxide, more superoxide, and less insulin‐like growth factor‐1 than wild‐type microglia. In microglia/motoneuron co‐cultures, mSOD1 G93A microglia induced more motoneuron death and decreased neurite numbers and length compared with wild‐type microglia. Mutant SOD1 G93A microglia also induced more motoneuron injury than microglia over‐expressing wild‐type human SOD1 in microglia/motoneuron co‐cultures. Motoneuron survival was inversely correlated with nitrate + nitrite concentrations in mSOD1 G93A co‐cultures, suggesting the important role of nitric oxide in microglia‐induced motoneuron injury. Thus, relative to wild‐type microglia, mSOD1 G93A microglia were more neurotoxic and induced more motoneuron injury than similarly treated wild‐type microglia.
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Pretreatment with L-NIL increased co-cultured motor neuron survival.
“Pretreatment with L-NIL, an inhibitor of iNOS, increased co-cultured motor neuron survival.506”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [506]
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- Authors
- Xiao, Q., Zhao, W., Beers, D. R., Yen, A. A., Xie, W., Henkel, J. S., & Appel, S. H.
- Affiliations
- Houston Methodist (US)
- Baylor College of Medicine (US)
- Corresponding author
- Appel, Stanley H.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-05
- Volume
- 102
- Issue
- 6
- Pages
- 2008-2019
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1981329326
- Cited by
- 174
- References
- 50
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 10 · 2020: 13 · 2019: 3 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 9 · 2013: 12 · 2012: 14
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS048950, R01NS048950)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- microglia, neurotoxicity, amyotrophic lateral sclerosis, motoneuron death, nitric oxide, superoxide, insulin-like growth factor I, lipopolysaccharide, neurite outgrowth, nitrite/nitrate
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Cell Communication, Cells, Cultured, Central Nervous System, Humans, Lipopolysaccharides, Mice, Transgenic, Motor Neurons, Mutation, Nerve Degeneration, Nitric Oxide, Superoxide Dismutase, Cell Death, Rats, Sprague-Dawley, Microglia, Oxidative Stress, Inflammation Mediators, Coculture Techniques, Mice, Rats
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