alpha-Tocopherol transfer protein inhibition is effective in the prevention of cerebral malaria in mice.
BACKGROUND
Nutritional status likely plays an important role in determining the outcome of protozoan infections. Despite the evidence of Plasmodium sensitivity to oxidative stress, the potential role of vitamin E, a free radical scavenger, on the outcome of cerebral malaria (CM) has yet to be elucidated.


OBJECTIVE
To determine the influence of vitamin E on Plasmodium parasite development and murine CM outcome, alpha-tocopherol transfer protein (alpha-TTP), a regulator of vitamin E in the host circulation, was abrogated.


METHODS
alpha-TTP knockout mice were infected with Plasmodium berghei ANKA, and survival rate, parasitemia, brain histologic alterations, and brain barrier permeability were assessed. In addition, mRNA expression of the cytokines and adhesion molecules involved in this neurologic pathology were monitored.


RESULTS
alpha-TTP knockout mice infected with P. berghei ANKA did not exhibit any clinical or pathologic signs of CM, and a histologic analysis of the brain tissues in these animals showed no alteration of blood-brain barrier integrity compared with that in control mice. Interestingly, protection of the blood-brain barrier in these infected alpha-TTP knockout mice was lost when dietary supplementation with vitamin E was added to their diet. Moreover, interleukins and adhesion molecule transcripts in the brain of control mice were significantly up-regulated compared with those in the alpha-TTP knockout mice.


CONCLUSIONS
It appears that a deficiency of alpha-tocopherol in the circulation prevents CM and suggests that alpha-TTP is a putative target for the early prevention of CM.
Herbas
Maria S
MS
Research Unit for Functional Genomics, National Research Center for Protozoan Diseases, Obihiro University of Agriculture, Tokyo, Japan.
Okazaki
Mikiko
M
Terao
Eri
E
Xuan
Xuenan
X
Arai
Hiroyuki
H
Suzuki
Hiroshi
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D016779:Malaria, Cerebral / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D010961:Plasmodium; D010962:Plasmodium berghei; D012333:RNA, Messenger / Q000235:genetics; D014801:Vitamin A / Q000097:blood; D014802:Vitamin A Deficiency / Q000235:genetics*; D014810:Vitamin E / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D012333:RNA, Messenger; C017763:alpha-tocopherol transfer protein; D014801:Vitamin A; D014810:Vitamin E