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Non-linear Effects of Cycloheximide in Glutamate-Treated Cultured Rat Cerebellar Neurons

Non-linear Effects of Cycloheximide in Glutamate-Treated Cultured Rat Cerebellar Neurons

Diane Marotta, Ann Marini, Krishna Banaudha, Susan Maharaj, John Ives, Craig R Morrissette, Wayne B Jonas

Neurotoxicology. 2002 Sep;23(3):307-12.

PMID: 12387359

Abstract:

Multiple cell types and organisms across a wide array of phyla and a variety of toxins demonstrate non-linear dose responses to low-level chemical exposures with high doses inhibiting cellular function and low doses stimulating function. We tested whether such non-linear responses to low and ultra-low dose N-methyl-D-aspartate (NMDA), 1-methyl-4-phenylpyridinium (MPP+) or cycloheximide moderated toxic glutamate exposure in cultured cerebellar granule cells. Neurons were incubated over 72 h with successive NMDA, MPP+ iodide or cycloheximide additions producing specified low (10(-5), 10(-7), 10(-9), 10(-11), and 10(-13) M) and ultra-low (10(-27),10(-29), 10(-63), and 10(-65) M) concentrations. Subsequently these neuronal cells were exposed to a 50% excitotoxic concentration of glutamate for 24 h. Neuronal viability was significantly reduced in neurons treated with micromolar (10(-5) M) cycloheximide whereas viability was enhanced in neurons treated with an ultra-low dose exposure of 10(-27) M cycloheximide. Neither NMDA nor MPP+ elicited harmful or protective responses. This is the first report demonstrating non-linear dose-response effects of cycloheximide in low and ultra-low concentration ranges.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP36913390	MPP+ iodide		36913-39-0	Price

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