title: Heterogeneous responses to antioxidants in noradrenergic neurons of the Locus coeruleus indicate differing susceptibility to free radical content.
abstract: The present study investigated the effects of the antioxidants trolox and dithiothreitol (DTT) on mouse Locus coeruleus (LC) neurons. Electrophysiological measurement of action potential discharge and whole cell current responses in the presence of each antioxidant suggested that there are three neuronal subpopulations within the LC. In current clamp experiments, most neurons (55%; 6/11) did not respond to the antioxidants. The remaining neurons exhibited either hyperpolarization and decreased firing rate (27%; 3/11) or depolarization and increased firing rate (18%; 2/11). Calcium and JC-1 imaging demonstrated that these effects did not change intracellular Ca(2+) concentration but may influence mitochondrial function as both antioxidant treatments modulated mitochondrial membrane potential. These suggest that the antioxidant-sensitive subpopulations of LC neurons may be more susceptible to oxidative stress (e.g., due to ATP depletion and/or overactivation of Ca(2+)-dependent pathways). Indeed it may be that this subpopulation of LC neurons is preferentially destroyed in neurological pathologies such as Parkinson's disease. If this is the case, there may be a protective role for antioxidant therapies.
authors.affiliation: School of Biomedical Sciences and Pharmacy, The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW 2308, Australia.
authors.forename: Ramatis B
authors.initials: RB
authors.lastname: de Oliveira
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Gravina
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.forename: Alan M
authors.initials: AM
authors.lastname: Brichta
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Callister
authors.forename: Dirk F
authors.initials: DF
authors.lastname: van Helden
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D059331:Adrenergic Neurons / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011522:Protons
chemical_list: D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D011522:Protons; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium; D004229:Dithiothreitol