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.
Desrumaux
Catherine
C
Laboratoire de Biochimie des Lipoprotéines, INSERM, Dijon, France.
Risold
Pierre-Yves
PY
Schroeder
Henri
H
Deckert
Valérie
V
Masson
David
D
Athias
Anne
A
Laplanche
Hélène
H
Le Guern
Naig
N
Blache
Denis
D
Jiang
Xian-Cheng
XC
Tall
Alan R
AR
Desor
Didier
D
Lagrost
Laurent
L
D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000503:physiopathology; D001008:Anxiety Disorders / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry; D005260:Female; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D020297:Mice, Congenic; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D049294:Phospholipid Transfer Proteins / Q000172:deficiency*; D014810:Vitamin E / Q000378:metabolism*
D015415:Biomarkers; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D014810:Vitamin E