Linked Life Data

21562267

Source:http://linkedlifedata.com/resource/pubmed/id/21562267

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2011-5-12
pubmed:abstractText
Liver X receptors (LXRs) regulate immune cell function and cholesterol metabolism, both factors that are critically involved in Alzheimer's disease (AD). To investigate the therapeutic potential of long-term LXR activation in amyloid-? (A?) peptide deposition in an AD model, 13-month-old, amyloid plaque-bearing APP23 mice were treated with the LXR agonist TO901317. Postmortem analysis demonstrated that TO901317 efficiently crossed the blood-brain barrier. Insoluble and soluble A? levels in the treated APP23 mice were reduced by 80% and 40%, respectively, compared with untreated animals. Amyloid precursor protein (APP) processing, however, was hardly changed by the compound, suggesting that the observed effects were instead mediated by A? disposal. Despite the profound effect on A? levels, spatial learning in the Morris water maze was only slightly improved by the treatment. ABCA1 (ATP-binding cassette transporter 1) and apolipoprotein E (ApoE) protein levels were increased and found to be primarily localized in astrocytes. Experiments using primary microglia demonstrated that medium derived from primary astrocytes exposed to TO901317 stimulated phagocytosis of fibrillar A?. Conditioned medium from TO901317-treated ApoE(-/-) or LXR?(-/-) astrocytes did not increase phagocytosis of A?. In APP23 mice, long-term treatment with TO901317 strongly increased the association of microglia and A? plaques. Short-term treatment of APP/PS1 mice with TO901317 also increased this association, which was dependent on the presence of LXR? and was accompanied by increased ApoE lipidation. Together, these data suggest that astrocytic LXR? activation and subsequent release of ApoE by astrocytes is critical for the ability of microglia to remove fibrillar A? in response to treatment with TO901317.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7049-59
pubmed:meshHeading
pubmed-meshheading:21562267-Amyloid beta-Peptides, pubmed-meshheading:21562267-Amyloid beta-Protein Precursor, pubmed-meshheading:21562267-Analysis of Variance, pubmed-meshheading:21562267-Animals, pubmed-meshheading:21562267-Apolipoproteins E, pubmed-meshheading:21562267-Astrocytes, pubmed-meshheading:21562267-Blood-Brain Barrier, pubmed-meshheading:21562267-Blotting, Western, pubmed-meshheading:21562267-Brain, pubmed-meshheading:21562267-Culture Media, Conditioned, pubmed-meshheading:21562267-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21562267-Hydrocarbons, Fluorinated, pubmed-meshheading:21562267-Immunoassay, pubmed-meshheading:21562267-Immunohistochemistry, pubmed-meshheading:21562267-Maze Learning, pubmed-meshheading:21562267-Mice, pubmed-meshheading:21562267-Mice, Transgenic, pubmed-meshheading:21562267-Microglia, pubmed-meshheading:21562267-Orphan Nuclear Receptors, pubmed-meshheading:21562267-Phagocytosis, pubmed-meshheading:21562267-Sulfonamides
pubmed:year
2011
pubmed:articleTitle
Critical role of astroglial apolipoprotein E and liver X receptor-? expression for microglial A? phagocytosis.
pubmed:affiliation
Department of Neurology, University of Bonn, 53127 Bonn, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural