title: Hydrogen peroxide differentially affects activity in the pre-Bötzinger complex and hippocampus.
abstract: Reactive oxygen species (ROS) modulate neuronal excitability. In the present study we examined the effects of hydrogen peroxide (H(2)O(2)), a well established ROS, on neuronal activity from two neonatal mouse brain regions, i.e., the pre-Bötzinger complex (preBötC) within the ventral respiratory column (VRC) and the CA1 area of the hippocampus. In the preBötC, 2.2 mM H(2)O(2) evoked a transient depression followed by augmentation of neuronal activity. The iron chelator deferoxamine (500 μM) did not prevent H(2)O(2)-mediated neuronal augmentation but prevented the initial depression. Combined application of Fe(2+) and H(2)O(2) only caused depression of the preBötC rhythm. In contrast, H(2)O(2) suppressed neuronal activity in the CA1 region, and this effect was accentuated by coapplication of Fe(2+) and H(2)O(2), suggesting that hydroxyl radical generated by Fenton reaction mediates the effects of H(2)O(2) on CA1 neuronal activity. Malondialdehyde (MDA) levels were monitored as an index of lipid peroxidation in H(2)O(2)-treated preBötC and CA1 areas. MDA levels were unaltered in H(2)O(2)-treated preBötC, whereas MDA levels were markedly elevated in the CA1 region. These findings suggest that 1) exogenous administration of H(2)O(2) exerts differential effects on neuronal activities of preBötC versus CA1 neuronal populations and 2) H(2)O(2) is a potent modulator of respiratory rhythmogenesis from the preBötC without affecting global oxidative status.
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, 1900 9th Ave., Seattle, WA, USA. alfredo.garcia@seattlechildrens.org
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Garcia
authors.forename: Shakil A
authors.initials: SA
authors.lastname: Khan
authors.forename: Ganesh K
authors.initials: GK
authors.lastname: Kumar
authors.forename: Nanduri R
authors.initials: NR
authors.lastname: Prabhakar
authors.forename: Jan-Marino
authors.initials: JM
authors.lastname: Ramirez
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D016877:Oxidants / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D012125:Respiratory Center / Q000166:cytology* / Q000187:drug effects; D017262:Siderophores / Q000494:pharmacology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003676:Deferoxamine; D018691:Excitatory Amino Acid Antagonists; D005296:Ferrous Compounds; D018756:GABA Antagonists; D006861:Hydrogen Peroxide; D008315:Malondialdehyde; D016877:Oxidants; D010852:Picrotoxin; D010879:Piperazines; D017262:Siderophores; C020748:ferrous sulfate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid