Vitamin E is essential for Purkinje neuron integrity.

ABSTRACT: ?-Tocopherol (vitamin E) is an essential dietary antioxidant with important neuroprotective functions. ?-Tocopherol deficiency manifests primarily in neurological pathologies, notably cerebellar dysfunctions such as spinocerebellar ataxia. To study the roles of ?-tocopherol in the cerebellum, we used the ?-tocopherol transfer protein for the murine version (Ttpa(-/)(-)) mice which lack the ?-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 ?-tocopherol in plasma and several brain regions. Dietary supplementation with ?-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 ?-tocopherol supplementation may comprise an effective intervention in oxidative stress-related neurological disorders.

SUBMITTER: Ulatowski L 

PROVIDER: S-EPMC3943241 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature