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.
|Number of pages||10|
|State||Published - Feb 28 2014|
Bibliographical noteFunding Information:
This work was supported by award DK067494 from the National Institutes of Health to D.M. We thank Dr. Sudha Iyenger of the Case Western Reserve University Department of Epidemiology and Biostatistics for expert statistical advice, and Katie Manjerovic and Dr. Gemma Casadesus-Smith of the Case Western Reserve University Rodent Behavioral Core for assistance in the behavior studies. The Axioplan microscope and Neurolucida software are housed in the Neurosciences imaging Core at Case Western Reserve University.
- Oxidative stress
- Purkinje neuron
- Vitamin E
ASJC Scopus subject areas
- Neuroscience (all)