Synergistic effects of low level stressors in an oxidative damage model of spinal motor neuron degeneration.
BACKGROUND
An increase in reactive oxygen species (ROS) burden and subsequent oxidative damage to nucleic acids, proteins, and lipids, occurs during the normal aging process of cells, including neurons.


OBJECTIVE
With this in mind we hypothesize that an oxidative stress which leads to an increased state of oxidation, but is not itself lethal, nonetheless renders the motor neuron more vulnerable to other sublethal stressors.


RESULTS
We have combined paraquat-induced oxidative stress with sublethal increased exogenous glutamate, or thermal stress, or a combination of both, and demonstrate a synergistic effect of low-level stressors on the viability of motor neurons.


CONCLUSIONS
This model of low-level oxidative stress reveals the subsequent vulnerability of motor neurons to genetic or environmental stressors and may in part explain the mid-life/late-life symptom onset in both familial and sporadic ALS patients.
Kriscenski-Perry
Elizabeth
E
Department of Neurology, University of Rochester School of Medicine & Dentistry, 601 Elmwood Avenue, Box 673, Rochester, NY 14642, USA.
Durham
Heather D
HD
Sheu
Shey-Shing
SS
Figlewicz
Denise A
DA
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000633:toxicity*; D006361:Heating; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity*; D018092:Kainic Acid Receptors / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018698:Glutamic Acid; D010269:Paraquat; D018092:Kainic Acid Receptors