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

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Desrumaux, Catherine, M | Risold, P. Y. | Schroeder, Henri | Deckert, Valérie | Masson, David | Athias, Anne | Laplanche, Hélène | Le Guern, Naig | Blache, Denis | Jiang, Xian Cheng | Tall, Alan | Desor, Didier | Lagrost, Laurent

Edité par CCSD ; Federation of American Society of Experimental Biology -

DOI: 10.1096/fj.04-2400fje. International audience. 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.

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