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Neuroprotection from glutamate toxicity with ultra-low dose glutamate

Jonas, WayneCA; Lin, Yu1; Tortella, Frank1

Neuropharmacology And Neurotoxicology

The protective effects of ultra-low doses (ULD) of glutamate against glutamate toxicity was studied in primary rat spinal, cortical and cerebellar neurons. Neurons were exposed to four subtoxic, ultra-low concentrations of glutamate (10−18 M, 10−20 M, 10−22 M and 10−30 M) for 72 h and then subsequently challenged with toxic concentrations (25 μM) of glutamate. Neuron viability was consistently 10% higher in spinal and cortical neurons pre-exposed to glutamate concentrations of 10−18 M and 10−22 M, and in cerebellar neurons pre-exposed to 10−20 M and 10−30 M. Using laser scanning confocal micro- scopy and the fluorescent calcium probe fluo-3, we found no alterations in intracellular calcium dynamics in the protected cells. This protective effect is consistent with a growing body of evidence for tolerance induced by low-dose toxin exposure but is the first time that such tolerance has been demonstrated with ultra-low glutamate exposure. Our data show that pre-exposure of neuronal cells to ULD glutamate can protect against subsequent exposure to toxic levels of glutamate.

Department of Family Medicine, Program in Neuroprotection, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814; 1Department of Neuropharmacology and Molecular Biology, Division of Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD, USA

CACorresponding Author

Received 18 October 2000; accepted 22 November 2000

© 2001 Lippincott Williams & Wilkins, Inc.