title: Nonlinear effects of glutamate and KCl on glutamate toxicity in cultured rat cerebellar neurons.
abstract: Nonlinear responses to toxin exposure have been observed in multiple cell types and organisms across a wide array of phyla. High dose toxin exposures inhibit or kill biological systems, while low dose exposures can stimulate survival mechanisms. We examined the effects of low (10(-3), 10(-5), 10(-7), and 10(-9) M) and ultra-low (10(-25) and 10(-61) M) KCl and glutamate pretreatment (72 h) against glutamate toxicity in rat cerebellar neurons. Ultra-low dilutions (10(-31), 10(-61), and 10(-401)) of an Arnica montana mother tincture were also investigated for their neuroprotective potentials. Viability was significantly enhanced in neurons pretreated with either 10(-3) M glutamate (10.6%) or 10(-9) M KCl (6.3%). None of the toxins evaluated displayed significant toxicity at the concentrations indicated. The protective effect of glutamate is likely mediated through activation of N-methyl-D-aspartate receptors, whereas low dose KCl might confer neuroprotection through enhanced alteration of Na+/K+ receptor dynamics. This is the first time high dose glutamate tolerance has been shown along with low dose KCl, and is consistent with previous reports demonstrating tolerance induced by low dose toxin exposure.
authors.affiliation: Samueli Institute for Information Biology, Program on Neuroprotection, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Marotta
authors.forename: Ann
authors.initials: A
authors.lastname: Marini
authors.forename: Krishna
authors.initials: K
authors.lastname: Banaudha
authors.forename: Susan V M
authors.initials: SV
authors.lastname: Maharaj
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Jonas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018650:Arnica; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000008:administration & dosage* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017711:Nonlinear Dynamics; D010936:Plant Extracts / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D018698:Glutamic Acid; D011189:Potassium Chloride