title: Altered selenium status in Huntington's disease: neuroprotection by selenite in the N171-82Q mouse model.
abstract: Disruption of redox homeostasis is a prominent feature in the pathogenesis of Huntington's disease (HD). Selenium an essential element nutrient that modulates redox pathways and has been reported to provide protection against both acute neurotoxicity (e.g. methamphetamine) and chronic neurodegeneration (e.g. tauopathy) in mice. The objective of our study was to investigate the effect of sodium selenite, an inorganic form of selenium, on behavioral, brain degeneration and biochemical outcomes in the N171-82Q Huntington's disease mouse model. HD mice, which were supplemented with sodium selenite from 6 to 14 weeks of age, demonstrated increased motor endurance, decreased loss of brain weight, decreased mutant huntingtin aggregate burden and decreased brain oxidized glutathione levels. Biochemical studies revealed that selenite treatment reverted HD-associated changes in liver selenium and plasma glutathione in N171-82Q mice and had effects on brain selenoprotein transcript expression. Further, we found decreased brain selenium content in human autopsy brain. Taken together, we demonstrate a decreased selenium phenotype in human and mouse HD and additionally show some protective effects of selenite in N171-82Q HD mice. Modification of selenium metabolism results in beneficial effects in mouse HD and thus may represent a therapeutic strategy.
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA; Neuroscience Graduate Program, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA; Neuroscience Graduate Program, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Marks
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA; Neuroscience Graduate Program, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Moline
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Barrows
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA.
authors.forename: Merl
authors.initials: M
authors.lastname: Raisbeck
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA.
authors.forename: Vanita
authors.initials: V
authors.lastname: Chopra
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hersch
authors.affiliation: Department of Veterinary Sciences, University of Wyoming, Laramie, WY 82070, USA; Neuroscience Graduate Program, University of Wyoming, Laramie, WY 82070, USA. Electronic address: jfox7@uwyo.edu.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Fox
mesh_terms: D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020887:Selenious Acid / Q000627:therapeutic use*; D012643:Selenium / Q000097:blood*; D016019:Survival Analysis; D013997:Time Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C497930:Ppp1r1b protein, rat; D020887:Selenious Acid; D012643:Selenium
keywords: Diet; Huntington's disease; Neurodegeneration; Neuroprotection; Selenium; Selenoprotein