“…The aging brain demonstrates region-specific alterations in neuronal morphology, reduced structural plasticity (30, 31) and dendritic branching (54), and a decreased capacity to regenerate (27, 55). With age the brain undergoes changes in plasma membrane biophysical properties (i.e., decreased cholesterol, gangliosides, and phosphoinositides) (56), impaired cholesterol synthesis and lipoprotein transport (55), changes in the molecular composition of the postsynaptic membrane (54) accompanied with reduced MLR-associated synaptic proteins (57), and diminished pre-synaptic vesicle exocytosis and subsequent neurotransmitter release; the latter are due to cholesterol depletion or cholesterol redistribution from cyto to exofacial leaflet of the plasma membrane ultimately leading to altered recruitment of SNARE complexes (56). Akin to these findings, previous work from our group demonstrated that Cav-1 and synaptic components (e.g., PSD-95, NMDAR, AMPAR, TrkB) are decreased in the aged brain, specifically in synaptosomes and MLRs isolated from the hippocampus (33, 54).…”