Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content and increases anxiety in mice.

Abstract

Vitamin E supplementation constitutes a promising strategy in the prevention of neurodegenerative diseases. Here, we show that a phospholipid transfer protein (PLTP) is widely expressed in the brain where it appears to function as a transfer factor for α‐tocopherol, the main isomer of vitamin E. PLTP deficiency results in significant depletion of brain α‐tocopherol in both homozygous (−30.1%, P <0.0002) and heterozygous (−18.0%, P <0.05) PLTP knocked‐out mice. α‐tocopherol depletion in PLTP‐deficient homozygotes is associated with the elevation of lipofuscin (+25% and +450% increases in cortex and substantia nigra, respectively), cholesterol oxides (+54.5%, P <0.05), and cellular peroxides (+32.3%, P <0.01) in the brain. Complete PLTP deficiency in homozygotes is accompanied by increased anxiety as shown by fewer entries (8.3% vs. 44.4% in controls, P <0.01) and less time spent (1.7% vs. 41.3% in controls, P <0.05) in the open arms of an elevated plus‐maze, in the absence of locomotor deterioration. Thus, the vitamin E transfer activity of PLTP appears to be a key process in preventing oxidative damage in the brain, and PLTP‐deficient mice could be a new model of the contribution of oxidative brain injury in the etiology of neurodegenerative diseases.