Neuroprotection from glutamate toxicity with ultra-low dose glutamate.
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 microM) 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 microscopy 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.
Jonas
W
W
Department of Family Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Lin
Y
Y
Tortella
F
F
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000633:toxicity*; D006705:Homeopathy; D007201:Indicator Dilution Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D018698:Glutamic Acid; D002118:Calcium