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

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 alpha-tocopherol, the main isomer of vitamin E. PLTP deficiency results in significant depletion of brain alpha-tocopherol in both homozygous ( - 30.1%, P< 0.0002) and heterozygous ( - 18.0%, P< 0.05) PLTP knocked-out mice. alpha-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.