title: Neither serotonin nor adenosine-dependent mechanisms preserve ventilatory capacity in ALS rats.
abstract: In rats over-expressing SOD1G93A, ventilation is preserved despite significant loss of respiratory motor neurons. Thus, unknown forms of compensatory respiratory plasticity may offset respiratory motor neuron cell death. Although mechanisms of such compensation are unknown, other models of respiratory motor plasticity may provide a conceptual guide. Multiple cellular mechanisms give rise to phrenic motor facilitation; one mechanism requires spinal serotonin receptor and NADPH oxidase activity whereas another requires spinal adenosine receptor activation. Here, we studied whether these mechanisms contribute to compensatory respiratory plasticity in SOD1G93A rats. Using plethysmography, we assessed ventilation in end-stage SOD1G93A rats after: (1) serotonin depletion with parachlorophenylalanine (PCPA), (2) serotonin (methysergide) and A2A (MSX-3) receptor inhibition, (3) NADPH oxidase inhibition (apocynin), and (4) combined treatments. The ability to increase ventilation was not decreased by individual or combined treatments; thus, these mechanisms do not maintain breathing capacity at end-stage motor neuron disease. Possible mechanisms giving rise to enhanced breathing capacity with combined treatment in end-stage SOD1G93A rats are discussed.
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706, United States.
authors.forename: N L
authors.initials: NL
authors.lastname: Nichols
authors.affiliation: Department of Surgical Sciences, University of Wisconsin, School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706, United States.
authors.forename: R A
authors.initials: RA
authors.lastname: Johnson
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706, United States.
authors.forename: I
authors.initials: I
authors.lastname: Satriotomo
authors.affiliation: Department of Comparative Biosciences, University of Wisconsin, School of Veterinary Medicine, 2015 Linden Drive, Madison, WI 53706, United States. Electronic address: mitchell@svm.vetmed.wisc.edu.
authors.forename: G S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010791:Phrenic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D058917:Adenosine A2 Receptor Antagonists; D004791:Enzyme Inhibitors; C113602:MSX 3 compound; C000606290:SOD1 protein, human; D012702:Serotonin Antagonists; D014970:Xanthines; D012701:Serotonin; C056165:acetovanillone; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; D000241:Adenosine; D008784:Methysergide
keywords: Compensatory plasticity; Facilitation; Plethysmography; Respiration