Loss of caveolin-1 accelerates neurodegeneration and aging

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Title Loss of caveolin-1 accelerates neurodegeneration and aging
Author Head, Brian P.; Peart, Jason Nigel John; Panneerselvam, Mathivadhani; Yokoyama, Takaakira; Pearn, Matthew L.; Niesman, Ingrid R.; Bonds, Jacqueline A.; Schilling, Jan M.; Miyanohara, Atsushi; Headrick, John Patrick; Ali, Sameh S.; Roth, David M.; Patel, Piyush M.; Patel, Hemal H.
Journal Name PLoS ONE
Year Published 2010
Place of publication United States
Publisher Public Library of Science
Abstract BACKGROUND: 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 Aβ, 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 Aβ expression. 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 disease
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1371/journal.pone.0015697
Copyright Statement Copyright 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)
Volume 5
Issue Number 12
Page from e15697-1
Page to e15697-13
ISSN 1932-6203
Date Accessioned 2011-04-20
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Clinical Pharmacology and Therapeutics
URI http://hdl.handle.net/10072/38250
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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