Differential effects of lovastatin treatment on brain cholesterol levels in normal and apoE-deficient mice.
Growing evidence indicates that membrane cholesterol is involved in the development of Alzheimer's disease. Therefore, the availability of pharmacological strategies to modify brain cholesterol is of increasing importance. Accordingly, we investigated the effects of the HMG-CoA reductase inhibitor lovastatin on brain cholesterol levels in vivo. Brain cholesterol was significantly decreased by lovastatin treatment (100 mg/kg/day) in 1- and 12-month-old C57BL/6J mice. Reduced brain cholesterol was associated with decreased pyrene-excimer fluorescence, indicating altered membrane function. Lovastatin had no effect on brain cholesterol ApoE-/- mice. Peripheral cholesterol levels were not affected by lovastatin in all three groups of mice. We demonstrate for the first time that lovastatin represents a valid pharmacological tool to significantly modulate brain cholesterol levels.
Eckert
G P
GP
Department of Pharmacology, Biocenter Niederursel, University of Frankfurt, Germany.
Kirsch
C
C
Mueller
W E
WE
D000375:Aging / Q000502:physiology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000172:deficiency*; D001923:Brain Chemistry / Q000187:drug effects*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011721:Pyrenes
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D005456:Fluorescent Dyes; D011721:Pyrenes; D002784:Cholesterol; D008148:Lovastatin