Age related decrease in post‐synaptic signaling components and caveolin‐1 in membrane/lipid rafts and synaptosomal membrane fractions in the CNS

Several synaptic resident proteins involved in neurotrophic signaling are compartmentalized to membrane/lipid (M/L) rafts. Their expression and localization to discrete microdomains is dependent on cholesterol binding and scaffolding protein caveolin (Cav). Consequently, Cav may serve to organize synaptosomal associated proteins within the M/L rafts and thus be a key mediator of protective neuronal signaling. We investigated the effect of aging on M/L raft protein composition. Sucrose density fractionation was performed on brains from three age groups of C57BL/6 mice: young (Yg), mature (Mat) and aged (Ag). The majority of Cav‐1 was detected in buoyant fractions (BFs) 4 and 5 of Yg brains. However, Cav‐1 was reduced in the BFs of Mt and Ag brains. IPs of Mt and Ag BFs showed a reduction in the co‐IP between Cav‐1 and PSD‐95 as well as almost no detection of NR2A, NR2B and AMPAR. Isolation of synaptosomal membranes from Yg Cav‐1 KO mice showed a reduction in PSD‐95 and NR subtypes compared to wild type. These findings demonstrate that cav expression and its ability to properly organize signaling complexes may be a key determinant of age related changes in synaptic and neuroprotective signaling.