Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration

Chonglun Xie, Erik G. Lund, Stephen D. Turley, David W. Russell, John M. Dietschy

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1780-1789
Number of pages10
JournalJournal of lipid research
Volume44
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Cholesterol 24-hydroxylase
  • Dementia
  • Glial cells
  • Neurons
  • Niemann-Pick type C disease
  • Oxysterols
  • Sterol 27-hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Fingerprint Dive into the research topics of 'Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration'. Together they form a unique fingerprint.

  • Cite this