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dc.contributor.authorP. Head, Brianen_US
dc.contributor.authorPeart, Jasonen_US
dc.contributor.authorPanneerselvam, Mathivadhanien_US
dc.contributor.authorYokoyama, Takaakiraen_US
dc.contributor.authorL. Pearn, Matthewen_US
dc.contributor.authorR. Niesman, Ingriden_US
dc.contributor.authorBonds, Jacqueline A.en_US
dc.contributor.authorM. Schilling, Janen_US
dc.contributor.authorMiyanohara, Atsushien_US
dc.contributor.authorHeadrick, Johnen_US
dc.contributor.authorS. Ali, Samehen_US
dc.contributor.authorM. Roth, Daviden_US
dc.contributor.authorM. Patel, Piyushen_US
dc.contributor.authorH. Patel, Hemalen_US
dc.date.accessioned2017-05-03T12:55:48Z
dc.date.available2017-05-03T12:55:48Z
dc.date.issued2010en_US
dc.date.modified2011-05-11T07:21:59Z
dc.identifier.issn19326203en_US
dc.identifier.doi10.1371/journal.pone.0015697en_AU
dc.identifier.urihttp://hdl.handle.net/10072/38250
dc.description.abstractBACKGROUND: The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased A߬ P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aߠexpression. CONCLUSIONS: Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's diseaseen_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.format.extent1514847 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherPublic Library of Scienceen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrome15697-1en_US
dc.relation.ispartofpagetoe15697-13en_US
dc.relation.ispartofissue12en_US
dc.relation.ispartofjournalPloS Oneen_US
dc.relation.ispartofvolume5en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchcode320503en_US
dc.titleLoss of caveolin-1 accelerates neurodegeneration and agingen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
dcterms.licensehttp://www.plos.org/journals/license.htmlen_US
gro.rights.copyrightCopyright 2010 Head et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)en_AU
gro.date.issued2010
gro.hasfulltextFull Text


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