title: Behavioral improvement after chronic administration of coenzyme Q10 in P301S transgenic mice.
abstract: Coenzyme Q10 is a key component of the electron transport chain which plays an essential role in ATP production and also has antioxidant effects. Neuroprotective effects of coenzyme Q10 have been reported in both in vitro and in vivo models of neurodegenerative diseases. However, its effects have not been studied in cells or in animals with tau induced pathology. In this report, we administered coenzyme Q10 to transgenic mice with the P301S tau mutation, which causes fronto-temporal dementia in man. These mice develop tau hyperphosphorylation and neurofibrillary tangles in the brain. Coenzyme Q10 improved survival and behavioral deficits in the P301S mice. There was a modest reduction in phosphorylated tau in the cortex of P301S mice. We also examined the effects of coenzyme Q10 treatment on the electron transport chain enzymes, the mitochondrial antioxidant enzymes, and the tricarboxylic acid cycle. There was a significant increase in complex I activity and protein levels, and a reduction in lipid peroxidation. Our data show that coenzyme Q10 significantly improved behavioral deficits and survival in transgenic mice with the P301S tau mutation, upregulated key enzymes of the electron transport chain, and reduced oxidative stress.
authors.affiliation: Weill Cornell Medical College, Department of Neurology and Neuroscience, New York, NY, USA.
authors.forename: Ceyhan
authors.initials: C
authors.lastname: Elipenahli
authors.forename: Cliona
authors.initials: C
authors.lastname: Stack
authors.forename: Shari
authors.initials: S
authors.lastname: Jainuddin
authors.forename: Meri
authors.initials: M
authors.lastname: Gerges
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: Anatoly
authors.initials: A
authors.lastname: Starkov
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Magali
authors.initials: M
authors.lastname: Dumont
mesh_terms: D000818:Animals; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects; D005260:Female; D057180:Frontotemporal Dementia / Q000378:metabolism* / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D016875:tau Proteins; D014451:Ubiquinone; C024989:coenzyme Q10