Differential effects of lovastatin treatment on brain cholesterol levels in normal and ApoE-deficient mice

被引：61

作者：

Eckert, GP ^{[1
]}

Kirsch, C ^{[1
]}

Mueller, WE ^{[1
]}

机构：

[1] Univ Frankfurt, Bioctr Niederursel, Dept Pharmacol, D-60439 Frankfurt, Germany

来源：

NEUROREPORT | 2001年 / 12卷 / 05期

关键词：

ApoE-deficient mice; brain cholesterol; lovastatin treatment;

D O I：

10.1097/00001756-200104170-00003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 in 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. NeuroReport 12:883-887 (C) 2001 Lippincott Williams & Wilkins.

引用

页码：883 / 887

页数：5

共 25 条

[1] Apolipoprotein E and β-amyloid levels in the hippocampus and frontal cortex of Alzheimer's disease subjects are disease-related and apolipoprotein E genotype dependent [J].

Beffert, U ;

Cohn, JS ;

Petit-Turcotte, C ;

Tremblay, M ;

Aumont, N ;

Ramassamy, C ;

Davignon, J ;

Poirier, J .

BRAIN RESEARCH, 1999, 843 (1-2) :87-94

[2] Importance of a novel oxidative mechanism for elimination of brain cholesterol - Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with O-18(2) techniques in vivo and in vitro [J].

Bjorkhem, I ;

Lutjohann, D ;

Breuer, O ;

Sakinis, A ;

Wennmalm, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (48) :30178-30184

[3]

Bodovitz S, 1996, J BIOL CHEM, V271, P4436

[4] Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus:: Specific changes in Alzheimer's disease [J].

Eckert, GP ;

Cairns, NJ ;

Maras, A ;

Gattaz, WF ;

Müller, WE .

DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2000, 11 (04) :181-186

[5] The role of cholesterol in the biosynthesis of β-amyloid. [J].

Frears, ER ;

Stephens, DJ ;

Walters, CE ;

Davies, H ;

Austen, BM .

NEUROREPORT, 1999, 10 (08) :1699-1705

[6] Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway [J].

Galbete, JL ;

Rodriguez-Martin, T ;

Peressini, E ;

Modena, P ;

Bianchi, R ;

Forloni, G .

BIOCHEMICAL JOURNAL, 2000, 348 :307-313

[7] APOLIPOPROTEIN-E AND CHOLESTEROL AFFECT NEURONAL CALCIUM SIGNALING - THE POSSIBLE RELATIONSHIP TO BETA-AMYLOID NEUROTOXICITY [J].

HARTMANN, H ;

ECKERT, A ;

MULLER, WE .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 200 (03) :1185-1192

[8]

Kalaria RN, 2000, ANN NY ACAD SCI, V903, P1

[9] Alzheimer's Aβ1-40 peptide modulates lipid synthesis in neuronal cultures and intact rat fetal brain under normoxic and oxidative stress conditions [J].

Koudinova, NV ;

Koudinov, AR ;

Yavin, E .

NEUROCHEMICAL RESEARCH, 2000, 25 (05) :653-660

[10] LIPID-LOWERING ACTIVITY OF ATORVASTATIN AND LOVASTATIN IN RODENT SPECIES - TRIGLYCERIDE-LOWERING IN RATS CORRELATES WITH EFFICACY IN LDL ANIMAL-MODELS [J].

KRAUSE, BR ;

NEWTON, RS .

ATHEROSCLEROSIS, 1995, 117 (02) :237-244

← 1 2 3 →