Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation.
We have investigated whether side chain-hydroxylated cholesterol species are important for elimination of cholesterol from the brain. Plasma concentrations of 24-hydroxycholesterol (24-OH-Chol) in the internal jugular vein and the brachial artery in healthy volunteers were consistent with a net flux of this steroid from the brain into the circulation, corresponding to elimination of approximately 4 mg cholesterol during a 24-h period in adults. Results of experiments with rats exposed to 18O2 were also consistent with a flux of 24-OH-Chol from the brain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concentration of 24-OH-Chol was 30- to 1500-fold higher in the brain than in any other organ except the adrenals indicate that the major part of 24-OH-Chol present in the circulation originates from the brain. Both the 24-OH-Chol present in the brain and in the circulation were the 24S-stereoisomer. In contrast to other oxysterols, levels of plasma 24-OH-Chol were found to be markedly dependent upon age. The ratio between 24-OH-Chol and cholesterol in plasma was approximately 5 times higher during the first decade of life than during the sixth decade. There was a high correlation between levels of 24-OH-Chol in plasma and cerebrospinal fluid. It is suggested that the flux of 24-OH-Chol from the brain is important for cholesterol homeostasis in this organ.
Lütjohann
D
D
Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Sweden.
Breuer
O
O
Ahlborg
G
G
Nennesmo
I
I
Sidén
A
A
Diczfalusy
U
U
Björkhem
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D005260:Female; D006706:Homeostasis; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007223:Infant; D008297:Male; D008875:Middle Aged; D010100:Oxygen; D051381:Rats; D012016:Reference Values; D013237:Stereoisomerism; D014018:Tissue Distribution
D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D010100:Oxygen