title: Vitamin E is essential for Purkinje neuron integrity.
abstract: α-Tocopherol (vitamin E) is an essential dietary antioxidant with important neuroprotective functions. α-Tocopherol deficiency manifests primarily in neurological pathologies, notably cerebellar dysfunctions such as spinocerebellar ataxia. To study the roles of α-tocopherol in the cerebellum, we used the α-tocopherol transfer protein for the murine version (Ttpa(-/)(-)) mice which lack the α-tocopherol transfer protein (TTP) and are a faithful model of vitamin E deficiency and oxidative stress. When fed vitamin E-deficient diet, Ttpa(-/)(-) mice had un-detectable levels of α-tocopherol in plasma and several brain regions. Dietary supplementation with α-tocopherol normalized plasma levels of the vitamin, but only modestly increased its levels in the cerebellum and prefrontal cortex, indicating a critical function of brain TTP. Vitamin E deficiency caused an increase in cerebellar oxidative stress evidenced by increased protein nitrosylation, which was prevented by dietary supplementation with the vitamin. Concomitantly, vitamin E deficiency precipitated cellular atrophy and diminished dendritic branching of Purkinje neurons, the predominant output regulator of the cerebellar cortex. The anatomic decline induced by vitamin E deficiency was paralleled by behavioral deficits in motor coordination and cognitive functions that were normalized upon vitamin E supplementation. These observations underscore the essential role of vitamin E and TTP in maintaining CNS function, and support the notion that α-tocopherol supplementation may comprise an effective intervention in oxidative stress-related neurological disorders.
authors.affiliation: Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ulatowski
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors.forename: R
authors.initials: R
authors.lastname: Parker
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: G
authors.initials: G
authors.lastname: Warrier
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Butterfield
authors.affiliation: Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: dxm178@case.edu.
authors.forename: D
authors.initials: D
authors.lastname: Manor
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014811:Vitamin E Deficiency / Q000473:pathology / Q000503:physiopathology; D024502:alpha-Tocopherol / Q000097:blood / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; C002744:3-nitrotyrosine; D014443:Tyrosine; D024502:alpha-Tocopherol
keywords: 3-NT; 3-nitrotyrosine; AD; ANOVA; AVED; Alzheimer’s disease; CS; NPC; Niemann Pick disease type C; Purkinje neuron; SCA; TBARS; TTP; TTPA; Ttpa; US; analysis of variance; ataxia; ataxia with vitamin E deficiency; cerebellum; conditioned stimulus; oxidative stress; spinocerebellar ataxia; t-HODE; thiobarbituric acid reactive substances; tocopherol; total hydroxyoctadecadienoic acid; unconditioned stimulus; vitamin E; α-tocopherol transfer protein; α-tocopherol transfer protein gene for the human version; α-tocopherol transfer protein gene for the murine version