TY - JOUR
T1 - Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration
AU - Xie, Chonglun
AU - Lund, Erik G.
AU - Turley, Stephen D.
AU - Russell, David W.
AU - Dietschy, John M.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Although the pool of cholesterol in the adult central nervous system (CNS) is large and of constant size, little is known of the process(es) involved in regulation of sterol turnover in this pool. In 7-week-old mice, net excretion of cholesterol from the brain equaled 1.4 mg/day/kg body weight, and from the whole animal was 179 mg/day/kg. Deletion of cholesterol 24-hydroxylase, an enzyme highly expressed in the CNS, did not alter brain growth or myelination, but reduced sterol excretion from the CNS 64% to 0.5 mg/day/kg. In mice with a mutation in the Niemann-Pick C gene that had ongoing neurodegeneration, sterol excretion from the CNS was increased to 2.3 mg/day/kg. Deletion of cholesterol 24-hydroxylase activity in these animals reduced net excretion only 22% to 1.8 mg/day/kg. Thus, at least two different pathways promote net sterol excretion from the CNS. One uses cholesterol 24-hydroxylase and may reflect sterol turnover in large neurons in the brain. The other probably involves the movement of cholesterol or one of its metabolites across the blood-brain barrier and may more closely mirror sterol turnover in pools such as glial cell membranes and myelin.-Xie C., E. G. Lund, S. D. Turley, D. W. Russell, and J. M. Dietschy. Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration.
AB - Although the pool of cholesterol in the adult central nervous system (CNS) is large and of constant size, little is known of the process(es) involved in regulation of sterol turnover in this pool. In 7-week-old mice, net excretion of cholesterol from the brain equaled 1.4 mg/day/kg body weight, and from the whole animal was 179 mg/day/kg. Deletion of cholesterol 24-hydroxylase, an enzyme highly expressed in the CNS, did not alter brain growth or myelination, but reduced sterol excretion from the CNS 64% to 0.5 mg/day/kg. In mice with a mutation in the Niemann-Pick C gene that had ongoing neurodegeneration, sterol excretion from the CNS was increased to 2.3 mg/day/kg. Deletion of cholesterol 24-hydroxylase activity in these animals reduced net excretion only 22% to 1.8 mg/day/kg. Thus, at least two different pathways promote net sterol excretion from the CNS. One uses cholesterol 24-hydroxylase and may reflect sterol turnover in large neurons in the brain. The other probably involves the movement of cholesterol or one of its metabolites across the blood-brain barrier and may more closely mirror sterol turnover in pools such as glial cell membranes and myelin.-Xie C., E. G. Lund, S. D. Turley, D. W. Russell, and J. M. Dietschy. Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration.
KW - Cholesterol 24-hydroxylase
KW - Dementia
KW - Glial cells
KW - Neurons
KW - Niemann-Pick type C disease
KW - Oxysterols
KW - Sterol 27-hydroxylase
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U2 - 10.1194/jlr.M300164-JLR200
DO - 10.1194/jlr.M300164-JLR200
M3 - Article
C2 - 12810827
AN - SCOPUS:0141459395
SN - 0022-2275
VL - 44
SP - 1780
EP - 1789
JO - Journal of lipid research
JF - Journal of lipid research
IS - 9
ER -