title: Disruption, but not overexpression of urate oxidase alters susceptibility to pentylenetetrazole- and pilocarpine-induced seizures in mice.
abstract: There is a continuous drive to find new, improved therapies that have a different mechanism of action in order to help diminish the sizable percentage of persons with pharmacoresistant epilepsy. Uric acid is increasingly recognized as contributing to the pathophysiology of multiple disorders, and there are indications that uric acid might play a role in epileptic mechanisms. Nevertheless, studies that directly investigate its involvement are lacking. In this study we assessed the susceptibility to pentylenetetrazole- and pilocarpine-induced seizures in mice with genetically altered uric acid levels by targeting urate oxidase, which is the enzyme responsible for uric acid breakdown. We found that although disruption of urate oxidase resulted in a decreased susceptibility to all behavioral end points in both seizure models, overexpression did not result in any alterations when compared to their wild-type littermates. Our results suggest that a chronic increase in uric acid levels may result in decreased brain excitability.
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Lisa
authors.initials: L
authors.lastname: Thyrion
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.|Center for Neurosciences, Department of Pharmaceutical Chemistry, Drug Analysis & Drug Information, Free University of Brussels, Brussels, Belgium.
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Portelli
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Robrecht
authors.initials: R
authors.lastname: Raedt
authors.affiliation: Nephrology Section, Department of Internal Medicine, Ghent University, Ghent, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Larsen
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Sprengers
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Van Lysebettens
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Carrette
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Delbeke
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Kristl
authors.initials: K
authors.lastname: Vonck
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology (LCEN3), Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000009:adverse effects*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010433:Pentylenetetrazole / Q000009:adverse effects*; D010862:Pilocarpine / Q000009:adverse effects*; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D014503:Urate Oxidase / Q000172:deficiency* / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism
chemical_list: D003292:Convulsants; D010862:Pilocarpine; D014527:Uric Acid; D014503:Urate Oxidase; D010433:Pentylenetetrazole
keywords: Mice; Pentylenetetrazole; Pilocarpine; Urate oxidase; Uric acid