Article

Dietary plant sterols accumulate in the brain.

Department of Molecular Cell Biology (Box 17), Research Institute Brain and Behaviour (EURON), University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Biochimica et Biophysica Acta (impact factor: 4.66). 05/2006; 1761(4):445-53. DOI:10.1016/j.bbalip.2006.03.015 pp.445-53
Source: PubMed

ABSTRACT Dietary plant sterols and cholesterol have a comparable chemical structure. It is generally assumed that cholesterol and plant sterols do not cross the blood-brain barrier, but quantitative data are lacking. Here, we report that mice deficient for ATP-binding cassette transporter G5 (Abcg5) or Abcg8, with strongly elevated serum plant sterol levels, display dramatically increased (7- to 16-fold) plant sterol levels in the brain. Apolipoprotein E (ApoE)-deficient mice also displayed elevated serum plant sterol levels, which was however not associated with significant changes in brain plant sterol levels. Abcg5- and Abcg8-deficient mice were found to carry circulating plant sterols predominantly in high-density lipoprotein (HDL)-particles, whereas ApoE-deficient mice accommodated most of their serum plant sterols in very low-density lipoprotein (VLDL)-particles. This suggests an important role for HDL and/or ApoE in the transfer of plant sterols into the brain. Moreover, sitosterol upregulated apoE mRNA and protein levels in astrocytoma, but not in neuroblastoma cells, to a higher extend than cholesterol. In conclusion, dietary plant sterols pass the blood-brain barrier and accumulate in the brain, where they may exert brain cell type-specific effects.

0 0
 · 
0 Bookmarks
 · 
41 Views
  • Source
    Article: Human apolipoprotein C-I expression in mice impairs learning and memory functions.
    Karlygash Abildayeva, Jimmy F P Berbée, Arjan Blokland, Paula J Jansen, Frans J Hoek, Onno Meijer, Dieter Lütjohann, Thomas Gautier, Thierry Pillot, Jan De Vente, Louis M Havekes, Frans C S Ramaekers, Folkert Kuipers, Patrick C N Rensen, Monique Mulder
    [show abstract] [hide abstract]
    ABSTRACT: The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD brains. Interestingly, apoC-I colocalized with beta-amyloid (Abeta) in plaques in AD brains, and in vitro experiments revealed that aggregation of Abeta was delayed in the presence of apoC-I. Moreover, apoC-I was found to exacerbate the soluble Abeta oligomer-induced neuronal death. To establish a potential role for apoC-I in cognitive functions, we used human (h) APOC1(+/0) transgenic mice that express APOC1 mRNA throughout their brains and apoC-I protein in astrocytes and endothelial cells. The hAPOC1(+/0) mice displayed impaired hippocampal-dependent learning and memory functions compared with their wild-type littermates, as judged from their performance in the object recognition task (P = 0.012) and in the Morris water maze task (P = 0.010). ApoC-I may affect learning as a result of its inhibitory properties toward apoE-dependent lipid metabolism. However, no differences in brain mRNA or protein levels of endogenous apoE were detected between transgenic and wild-type mice. In conclusion, human apoC-I expression impairs cognitive functions in mice independent of apoE expression, which supports the potential of a modulatory role for apoC-I during the development of AD.
    The Journal of Lipid Research 05/2008; 49(4):856-69. · 5.56 Impact Factor
  • Source
    Article: Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE-/- mice.
    Oliver Weingärtner, Christof Ulrich, Dieter Lütjohann, Kenan Ismail, Stephan H Schirmer, Tim Vanmierlo, Michael Böhm, Ulrich Laufs
    [show abstract] [hide abstract]
    ABSTRACT: 'Functional foods' supplemented with plant sterol esters (PSE) and plant stanol esters (PSA) are therapeutic options for the management of hypercholesterolaemia. However, their effects on blood monocytes, endothelial function, atherogenesis, and sterol tissue concentrations are poorly understood. Male apoE-/- mice (n= 30) were randomized to three different diets for 6 weeks (n= 10 per group): high-cholesterol (1.25%) western-type diet (WTD), WTD + 2% PSE, and WTD + 2% PSA. Both supplements reduced serum cholesterol. WTD + PSE resulted in increased plant sterol serum concentrations and increased inflammatory Ly-6C(high) monocyte numbers. WTD + PSA increased plant stanol serum concentrations and Ly-6C-monocyte numbers, but decreased vascular superoxide release, lipid hydroperoxides, and inflammatory cytokines in aortic tissue, in plasma, and in circulating monocytes. Despite reduced serum cholesterol concentrations, both supplements impaired endothelial vasodilation compared with WTD. WTD + PSA reduced the development of atherosclerotic lesions compared with WTD alone (12.7 ± 3.7 vs. 28.3 ± 3.5%), and WTD + PSE was less effective (17.5 ± 3.7%). WTD + PSE and WTD + PSA reduced the cholesterol content in the liver, but not in the brain. However, WTD + PSE and WTD + PSA increased plant sterol and plant stanol concentrations in the liver as well as in the brain. PSE and PSA supplementation reduced serum cholesterol, but increased plant sterol and plant stanol concentrations. Elevated levels of PSE and PSA were associated with endothelial dysfunction and increased central nervous system depositions. Atherosclerotic lesion retardation was more pronounced in WTD + PSA, coinciding with higher regenerative monocyte numbers, decreased oxidative stress, and decreased inflammatory cytokines compared with WTD + PSE.
    Cardiovascular research 02/2011; 90(3):484-92. · 5.80 Impact Factor
  • Source
    Article: Cerebral accumulation of dietary derivable plant sterols does not interfere with memory and anxiety related behavior in Abcg5-/- mice.
    Tim Vanmierlo, Kris Rutten, Leonie C van Vark-van der Zee, Silvia Friedrichs, Vincent W Bloks, Arjan Blokland, Frans C Ramaekers, Eric Sijbrands, Harry Steinbusch, Jos Prickaerts, Folkert Kuipers, Dieter Lütjohann, Monique Mulder
    [show abstract] [hide abstract]
    ABSTRACT: Plant sterols such as sitosterol and campesterol are frequently applied as functional food in the prevention of atherosclerosis. Recently, it became clear that plasma derived plant sterols accumulate in murine brains. We questioned whether plant sterols in the brain are associated with alterations in brain cholesterol homeostasis and subsequently with brain functions. ATP binding cassette (Abc)g5-/- mice, a phytosterolemia model, were compared to Abcg5+/+ mice for serum and brain plant sterol accumulation and behavioral and cognitive performance. Serum and brain plant sterol concentrations were respectively 35-70-fold and 5-12-fold increased in Abcg5-/- mice (P<0.001). Plant sterol accumulation resulted in decreased levels of desmosterol (P<0.01) and 24(S)-hydroxycholesterol (P<0.01) in the hippocampus, the brain region important for learning and memory functions, and increased lanosterol levels (P<0.01) in the cortex. However, Abcg5-/- and Abcg5+/+ displayed no differences in memory functions or in anxiety and mood related behavior. The swimming speed of the Abcg5-/- mice was slightly higher compared to Abcg5+/+ mice (P<0.001). In conclusion, plant sterols in the brains of Abcg5-/- mice did have consequences for brain cholesterol metabolism, but did not lead to an overt phenotype of memory or anxiety related behavior. Thus, our data provide no contra-indication for nutritional intake of plant sterol enriched nutrition.
    Materiae Vegetabiles 03/2011; 66(2):149-56. · 2.51 Impact Factor

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Abcg8-deficient mice
 
ApoE)-deficient mice
 
ApoE-deficient mice accommodated
 
Apolipoprotein E
 
ATP-binding cassette transporter G5
 
blood-brain barrier
 
brain plant sterol levels
 
comparable chemical structure
 
Dietary plant sterols
 
HDL)-particles
 
high-density lipoprotein
 
low-density lipoprotein
 
mice deficient
 
plant sterols
 
protein levels
 
quantitative data
 
serum plant sterol levels
 
serum plant sterols
 
significant changes
 
sitosterol upregulated apoE mRNA