Abstract
Elevation of intracellular calcium levels [Ca2+]i induces microtubule depolymerization, a process which plays roles in regulation of cell motility and axonal transport. However, excessive Ca2+ influx, as occurs in neurons subjected to excitotoxic conditions, can kill neurons. We now provide evidence that the polymerization state of microtubules influences neuronal [Ca2+]i homeostasis and vulnerability to excitotoxicity. The microtubule-stabilizing agent taxol significantly attenuated glutamate neurotoxicity in cultured rat hippocampal neurons. Experiments in which [Ca2+]i was monitored using the Ca2+ indicator dye fura-2 showed that the elevation of [Ca2+]i induced by glutamate was significantly attenuated in neurons pretreated with taxol. Experiments using selective glutamate receptor agonists suggested that taxol suppressed Ca2+ influx through α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, but not through N-methyl-D-aspartate (NMDA) receptors. Taxol attenuated the neurotoxicity of the microtubule-depolymerizing agent colchicine; colchicine neurotoxicity was, in part, dependent on Ca2+ influx. These findings suggest that microtobules play a role in the mechanism of excitotoxicity and suggest that taxol and related compounds may be useful as antiexcitotoxic agents.
Original language | English (US) |
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Pages (from-to) | 141-146 |
Number of pages | 6 |
Journal | Brain Research |
Volume | 689 |
Issue number | 1 |
DOIs | |
State | Published - Aug 14 1995 |
Externally published | Yes |
Keywords
- Alzheimer's disease
- Calcium
- Colchicine
- Excitototoxicity
- Fura-2
- Glutamate
- Microtubule
- Taxol
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- General Neuroscience