Cited by 81Neuroscience and Neuropharmacology ResearchCellular Mechanics and InteractionsIon channel regulation and function

Evidence That Actin Depolymerization Protects Hippocampal Neurons against Excitotoxicity by Stabilizing [Ca2+]i

Furukawa, Katsutoshi, Smith-Swintosky, Virginia L., Mattson, Mark P.·1995·Experimental Neurology

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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Crossref · 10.1006/exnr.1995.1018

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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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