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

DOI: 10.1096/fj.04-2400fjeInternational audienceVitamin 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