Cited by 122Antioxidant Activity and Oxidative StressNeurological Disease Mechanisms and TreatmentsGenetic Neurodegenerative Diseases

Vitamin E is essential for Purkinje neuron integrity

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Ulatowski, L., Parker, R., Warrier, G., Sultana, R., Butterfield, D.A., Manor, D.·2014·Neuroscience

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.

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Authors
Ulatowski, L., Parker, R., Warrier, G., Sultana, R., Butterfield, D. A., & Manor, D.
Affiliations
  • Case Western Reserve University (US)
  • Cornell University (US)
  • University of Kentucky (US)
Corresponding author
Manor, D.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2014-02
Volume
260
Pages
120-129
ISSN
0306-4522 (ISSN-L)
OpenAlex
W1972998914
Cited by
122
References
87
Citations by year
2026: 4 · 2025: 4 · 2024: 5 · 2023: 10 · 2022: 10 · 2021: 16 · 2020: 11 · 2019: 11 · 2018: 12 · 2017: 10 · 2016: 15 · 2015: 7 · 2014: 5 · 2013: 1 · 2012: 1
FWCI
6.96
Type
journal article
Language
en
Open access
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (2r01dk067494-07)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 067494, R01-DK067494)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
vitamin E, alpha-tocopherol, alpha-tocopherol transfer protein, vitamin E deficiency, cerebellum, Purkinje cells, oxidative stress, protein nitrosylation, dendritic branching, neuronal atrophy, spinocerebellar ataxia, motor coordination, cognitive impairment, dietary supplementation, neuroprotection
MeSH terms
Animals, Carrier Proteins, Cerebellum, Motor Activity, Purkinje Cells, Tyrosine, Vitamin E Deficiency, Prefrontal Cortex, Mice, Knockout, Oxidative Stress, alpha-Tocopherol, Mice

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