Evidence That Actin Depolymerization Protects Hippocampal Neurons against Excitotoxicity by Stabilizing [Ca2+]i
Abstract
Calcium influx through glutamate receptors and voltage-dependent channels mediates an array of functional and structural responses in neurons. However, unrestrained Ca2+ influx can injure and kill neurons; a mechanism implicated in both acute and chronic neurodegenerative disorders. Data reported here indicate that depolymerization of actin filaments can stabilize intracellular free calcium levels ([Ca2+]i) and protect hippocampal neurons against excitotoxic injury. Studies with fluorescein-labeled phalloidin showed that cytochalasin D and glutamate each induced actin filament depolymerization. The microfilament-disrupting agent cytochalasin D protected cultured rat hippocampal neurons against glutamate toxicity, whereas the actin filament-stabilizing agent jasplakinolide potentiated glutamate toxicity. The microtubule-disrupting agent colchicine was ineffective in protecting neurons against glutamate toxicity. Cytochalasin D did not protect neurons against calcium ionophore toxicity or iron toxicity, indicating that its actions were not due to nonspecific effects on Ca2+ or free radical metabolism. Cytochalasin D markedly attenuated kainate-induced damage to hippocampus of adult rats, suggesting an excitoprotective role for actin depolymerization in vivo. Elevations of [Ca2+]i induced by glutamate were attenuated in cultured hippocampal neurons pretreated with cytochalasin D and potentiated in neurons pretreated with jasplakinolide. The [Ca2+]i response to a Ca2+ ionophore w…
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Disruption of F-actin in cultured neurons attenuates excitotoxic cell death.
“Disruption of F-actin in cultured neurons has been shown to attenuate excitotoxic cell death (Furukawa et al., 1995).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Furukawa et al., 1995
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Self-citation
- Authors
- Furukawa, K., Smith-Swintosky, V. L., & Mattson, M. P.
- Affiliations
- University of Kentucky (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 1995-06
- Volume
- 133
- Issue
- 2
- Pages
- 153-163
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2066300012
- Cited by
- 81
- References
- 0
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2015: 3 · 2014: 4 · 2012: 1
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- actin depolymerization, excitotoxicity, hippocampal neurons, intracellular calcium, cytochalasin D, jasplakinolide, glutamate excitotoxicity, calcium influx, neuroprotection, kainic acid, F-actin
- MeSH terms
- Actins, Animals, Calcium, Cells, Cultured, Cytochalasins, Drug Synergism, Hippocampus, Intracellular Membranes, Male, Neurons, Neurotoxins, Osmolar Concentration, Peptides, Cyclic, Polymers, Rats, Sprague-Dawley, Neuroprotective Agents, Glutamic Acid, Depsipeptides, Rats
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