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Aged‐related decrease in post‐synaptic signaling components and caveolin‐1 in membrane/lipid rafts and synaptosomal membrane fractions in CNS
Author(s) -
Head Brian Patrick,
Bonds Jacqueline A.,
Roth David M.,
Patel Piyush M.,
Peart Jason N.,
Patel Hemal H.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.811.2
Subject(s) - lipid raft , ampa receptor , synaptosome , synaptic plasticity , microbiology and biotechnology , glutamate receptor , chemistry , biology , endocrinology , biochemistry , signal transduction , receptor , membrane
Spines/synaptic densities decreases in aged brains. Membrane/lipid rafts (MLRs), enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for development/stabilization of synapses. Caveolin (Cav), a cholesterol binding protein and marker of MRLs, localize synaptic residents such as NMDARs and AMPARs to MRLs, suggesting Cav compexes with synaptosomal proteins. We assessed age‐related loss of synaptic components from MLRs and synaptosomes (Syn). Two different sucrose density fractionation methods were used to isolate MLRs and Syn from brains of wild type (WT) C57BL/6 mice [young (Yg, 3‐6 months), mature (Mt, 12 months), and aged (Ag, 24 months)] and Cav‐1 KO mice (Yg). PSD‐95 (post‐synaptic density marker), the ionotropic glutamate receptors NMDAR2A (NR2A), NR2B, AMPAR, and Cav‐1 were detected in MLRs from Yg brains, with less detection in MLRs from Mt and Ag brains. Cav‐1 and PSD‐95 immunoprecipitation (IP) of MLRs showed a decrease in NR2A, NR2B, AMPAR, PSD‐95 and Cav‐1 in both IPs from Mt and Ag MLRs compared to Yg. There was also a significant decrease in PSD‐95, NR2A, NR2B, and Cav‐1 in Syn and PSD‐95 IPs of Syn with age. Hippocampi Syn from Cav‐1 KO mice (Yg) showed reduced PSD95, NR2A, and Cav‐1 compared to WT (Yg). These data indicate that Cav‐1 expression and its ability to properly organize signaling complexes may be a key determinant of age‐related changes in synaptic signaling.