title: Transient oxidative stress evokes early changes in the functional properties of neonatal rat hypoglossal motoneurons in vitro.
abstract: Oxidative stress of motoneurons is believed to be an important contributor to neurodegeneration underlying the familial (and perhaps even the sporadic) form of amyotrophic lateral sclerosis (ALS). This concept has generated numerous rodent genetic models with inborn oxidative stress to mimic the clinical condition. ALS is, however, a predominantly sporadic disorder probably triggered by environmental causes. Thus, it is interesting to understand how wild-type motoneurons react to strong oxidative stress as this response might cast light on the presymptomatic disease stage. The present study used, as a model, hypoglossal motoneurons from the rat brainstem slice to investigate how hydrogen peroxide could affect synaptic transmission and intrinsic motoneuron excitability in relation to their survival. Hydrogen peroxide (1 mm; 30 min) induced inward current or membrane depolarization accompanied by an increase in input resistance, enhanced firing and depressed spontaneous synaptic events. Despite enhanced intracellular oxidative processes, there was no death of motoneurons, although most cells were immunopositive for activating transcription factor 3, a stress-related transcription factor. Voltage-clamp experiments indicated increased frequency of excitatory or inhibitory miniature events, and reduced voltage-gated persistent currents of motoneurons. The global effect of this transient oxidative challenge was to depress the input flow from the premotor interneurons to motoneurons that became more excitable due to a combination of enhanced input resistance and impaired spike afterhyperpolarization. Our data show previously unreported changes in motoneuron activity associated with cell distress caused by a transient oxidative insult.
authors.affiliation: Neurobiology Sector, International School for Advanced Studies (SISSA), Via Beirut 2-4, 34151 Trieste, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cifra
authors.forename: Andrea
authors.initials: A
authors.lastname: Nistri
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D001933:Brain Stem / Q000166:cytology*; D002470:Cell Survival; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013331:Strychnine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D016900:Neurofilament Proteins; D017382:Reactive Oxygen Species; D026941:Sodium Channel Blockers; C051774:neurofilament protein H; D013779:Tetrodotoxin; D019284:Thapsigargin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D006861:Hydrogen Peroxide; D013331:Strychnine; D014633:Valine; D001640:Bicuculline