title: Cerium oxide nanoparticles with antioxidant properties ameliorate strength and prolong life in mouse model of amyotrophic lateral sclerosis.
abstract: Cerium oxide nanoparticles (CeNPs) neutralize reactive oxygen and nitrogen species. Since oxidative stress plays a role in amyotrophic lateral sclerosis (ALS) in humans and in the SOD1G93Amouse model of ALS, we tested whether administration of CeNPs would improve survival and reduce disease severity in SOD1G93Atransgenic mice. Twice a week intravenous treatment of SOD1G93Amice with CeNPs started at the onset of muscle weakness preserved muscle function and increased longevity in males and females. Median survival after the onset of CeNP treatment was 33.0±3.7days (N=20), and only 22.0±2.5days in mice treated with vehicle, control injections (N=27; P=0.022). Since these citrate-EDTA stabilized CeNPs exhibited catalase and oxidase activity in cell-free systems and in in vitro models of ischemic oxidative stress, we hypothesize that antioxidant activity is the protective mechanism prolonging survival in the SOD1G93Amice.
authors.affiliation: Department of Psychology, St. Lawrence University, Canton, NY, USA.
authors.forename: William
authors.initials: W
authors.lastname: DeCoteau
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Heckman
authors.affiliation: Department of Psychology, St. Lawrence University, Canton, NY, USA; Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Ana Y
authors.initials: AY
authors.lastname: Estevez
authors.affiliation: Cerion Enterprises, LLC, Rochester, NY, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Reed
authors.affiliation: Cerion Enterprises, LLC, Rochester, NY, USA.
authors.forename: Wendi
authors.initials: W
authors.lastname: Costanzo
authors.affiliation: Cerion Enterprises, LLC, Rochester, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sandford
authors.affiliation: Department of Psychology, St. Lawrence University, Canton, NY, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Studlack
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Clauss
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Nichols
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lipps
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Parker
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Hays-Erlichman
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. Electronic address: james.c.leiter@dartmouth.edu.
authors.forename: J C
authors.initials: JC
authors.lastname: Leiter
authors.affiliation: Department of Biology, St. Lawrence University, Canton, NY, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Erlichman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002563:Cerium / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002563:Cerium; C030583:ceric oxide; D010088:Oxidoreductases; D002374:Catalase
keywords: Amyotrophic lateral sclerosis; Cerium oxide nanoparticles; Oxidative stress