Preconditioning induces tolerance by suppressing glutamate release in neuron culture ischemia models
Article first published online: 1 JUN 2012
© 2012 National Research Council Canada. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 122, Issue 2, pages 470–481, July 2012
How to Cite
Tauskela, J. S., Aylsworth, A., Hewitt, M., Brunette, E. and Mealing, G. A. R. (2012), Preconditioning induces tolerance by suppressing glutamate release in neuron culture ischemia models. Journal of Neurochemistry, 122: 470–481. doi: 10.1111/j.1471-4159.2012.07791.x
- Issue published online: 2 JUL 2012
- Article first published online: 1 JUN 2012
- Accepted manuscript online: 19 MAY 2012 10:20AM EST
- Received April 13, 2012; revised manuscript received May 14, 2012; accepted May 16, 2012.
- synaptic scaling;
J. Neurochem. (2012) 122, 470–481.
This study determined how preconditioned neurons responded to oxygen-glucose deprivation (OGD) to result in neuroprotection instead of neurotoxicity. Neurons preconditioned using chronically elevated synaptic activity displayed suppressed elevations in extracellular glutamate ([glutamateex]) and intracellular Ca2+ (Ca2+in) during OGD. The glutamate uptake inhibitor TBOA induced neurotoxicity, but at a longer OGD duration for preconditioned cultures, suggestive of delayed up-regulation of transporter activity relative to non-preconditioned cultures. This delay was attributed to a critically attenuated release of glutamate, based on tolerance observed against insults mimicking key neurotoxic signaling during OGD (OGD-mimetics). Specifically, in the presence of TBOA, preconditioned neurons displayed potent protection to the OGD-mimetics: ouabain (a Na+/K+ ATPase inhibitor), high 55 mM KCl extracellular buffer (plasma membrane depolarization), veratridine (a Na+ ionophore), and paraquat (intracellular superoxide producer), which correlated with suppressed [glutamateex] elevations in the former two insults. Tolerance by preconditioning was reversed by manipulations that increased [glutamateex], such as by exposure to TBOA or GABAA receptor agonists during OGD, or by exposure to exogenous NMDA or glutamate. Pre-synaptic suppression of neuronal glutamate release by preconditioning, possibly via suppressed exocytic release, represents a key convergence point in neuroprotection during exposure to OGD and OGD-mimetics.