beta-Amyloid toxicity in organotypic hippocampal cultures: Protection by EUK-8, a synthetic catalytic free radical scavenger
Open accessAbstract
Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover, mature slices exposed to beta-AP in the presence of 25 microM EUK-8 were significantly protected from beta-AP-induced neurotoxicity. EUK-8 also completely blocked beta-AP-induced free radical accumulation and lipid peroxidation. These results not only support a role for oxygen free radicals in beta-AP toxicity but also highlight the therapeutic potential of synthetic radical scavengers in Alzheimer disease.
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“Studies have also rep rted that antioxidants protect against Aβ induced neuronal toxicity [16,17].”
BackgroundCognitive impairment in humanized APP×PS1 mice is linked to Aβ1–42 and NOX activation
Bruce-Keller, A. J., Gupta, S., Knight, A. G., Beckett, T. L., McMullen, J. M., Davis, P. R., Murphy, M. P., Van Eldik, L. J., St Clair, D., & Keller, J. N. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.07.012 · Cited by 96 · see citing works
- Authors
- Bruce, A. J., Malfroy, B., & Baudry, M.
- Affiliations
- Neuroscience Program, University of Southern California, Los Angeles 90089-2520, USA.
- University of Southern California (US)
- ORCID
- Baudry, M
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-03-19
- Volume
- 93
- Issue
- 6
- Pages
- 2312-2316
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39792
- OpenAlex
- W2132787891
- Cited by
- 216
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 8 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 9.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- amyloid-beta, neurotoxicity, superoxide scavengers, oxygen free radicals, reactive oxygen species, lipid peroxidation, hippocampal slice cultures, neuronal injury, Alzheimer's disease
- MeSH terms
- Animals, Biological Transport, Cell Membrane Permeability, Ethylenediamines, Hippocampus, L-Lactate Dehydrogenase, Organometallic Compounds, Oxidation-Reduction, Propidium, Free Radical Scavengers, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Reactive Oxygen Species, Culture Techniques, Rats
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