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http://hdl.handle.net/1942/30268
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DC Field | Value | Language |
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dc.contributor.author | Heneka, Michael T | - |
dc.contributor.author | Sastre, Magdalena | - |
dc.contributor.author | Dumitrescu-Ozimek, Lucia | - |
dc.contributor.author | Hanke, Anne | - |
dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Kuiperi, Cuno | - |
dc.contributor.author | O'Banion, Kerry | - |
dc.contributor.author | Klockgether, Thomas | - |
dc.contributor.author | Van Leuven, Fred | - |
dc.contributor.author | Landreth, Gary E | - |
dc.date.accessioned | 2020-01-09T12:42:27Z | - |
dc.date.available | 2020-01-09T12:42:27Z | - |
dc.date.issued | 2005 | - |
dc.date.submitted | 2020-01-09T12:08:13Z | - |
dc.identifier.issn | 0006-8950 | - |
dc.identifier.uri | http://hdl.handle.net/1942/30268 | - |
dc.description.abstract | Neuritic plaques in the brain of Alzheimer's disease patients are characterized by beta-amyloid deposits associated with a glia-mediated inflammatory response. Non-steroidal anti-inflammatory drug (NSAID) therapy reduces Alzheimer's disease risk and ameliorates microglial reactivity in Alzheimer's disease brains; however, the molecular mechanisms subserving this effect are not yet clear. Since several NSAIDs bind to and activate the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) which acts to inhibit the expression of proinflammatory genes, this receptor appears a good candidate to mediate the observed anti-inflammatory effects. Recent data in vitro suggested that NSAIDs negatively regulate microglial activation and immunostimulated amyloid precursor protein processing via PPARgamma activation. We report that an acute 7 day oral treatment of 10-month-old APPV717I mice with the PPARgamma agonist pioglitazone or the NSAID ibuprofen resulted in a reduction in the number of activated microglia and reactive astrocytes in the hippocampus and cortex. Drug treatment reduced the expression of the proinflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS). In parallel to the suppression of inflammatory markers, pioglitazone and ibuprofen treatment decreased beta-secretase-1 (BACE1) mRNA and protein levels. Importantly, we observed a significant reduction of the total area and staining intensity of Abeta1-42-positive amyloid deposits in the hippocampus and cortex. Additionally, animals treated with pioglitazone revealed a 27% reduction in the levels of soluble Abeta1-42 peptide. These findings demonstrate that anti-inflammatory drugs can act rapidly to inhibit inflammatory responses in the brain and negatively modulate amyloidogenesis. | - |
dc.description.sponsorship | This study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB 4000, A8) to M.T.H. and T.K., and the NIH (AG 16740, AG008012), the Blanchett Hooker Rockefeller Foundation and the CART Fund of Rotary International to G.L. | - |
dc.language.iso | en | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.rights | The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org | - |
dc.subject.other | Alzheimer’s disease | - |
dc.subject.other | PPAR | - |
dc.subject.other | inflammation | - |
dc.subject.other | NSAID | - |
dc.subject.other | neurodegeneration | - |
dc.title | Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice | - |
dc.type | Research Report | - |
dc.identifier.epage | 1453 | - |
dc.identifier.issue | Part 6 | - |
dc.identifier.spage | 1442-53 | - |
dc.identifier.volume | 128 | - |
local.bibliographicCitation.jcat | A1 | - |
local.publisher.place | GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Research Report | - |
dc.source.type | Article | - |
dc.identifier.doi | 10.1093/brain/awh452 | - |
dc.identifier.pmid | 15817521 | - |
dc.identifier.isi | 000229285700024 | - |
dc.identifier.eissn | 1460-2156 | - |
local.provider.type | PubMed | - |
local.uhasselt.uhpub | no | - |
item.fullcitation | Heneka, Michael T; Sastre, Magdalena; Dumitrescu-Ozimek, Lucia; Hanke, Anne; DEWACHTER, Ilse; Kuiperi, Cuno; O'Banion, Kerry; Klockgether, Thomas; Van Leuven, Fred & Landreth, Gary E (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. | - |
item.fulltext | With Fulltext | - |
item.accessRights | Closed Access | - |
item.contributor | Heneka, Michael T | - |
item.contributor | Sastre, Magdalena | - |
item.contributor | Dumitrescu-Ozimek, Lucia | - |
item.contributor | Hanke, Anne | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Kuiperi, Cuno | - |
item.contributor | O'Banion, Kerry | - |
item.contributor | Klockgether, Thomas | - |
item.contributor | Van Leuven, Fred | - |
item.contributor | Landreth, Gary E | - |
crisitem.journal.issn | 0006-8950 | - |
crisitem.journal.eissn | 1460-2156 | - |
Appears in Collections: | Research publications |
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