A role for caveolin‐1 in post‐injury reactive neuronal plasticity

Abstract Remodeling and plasticity in the adult brain require cholesterol redistribution and synthesis for the formation of new membrane components. Caveolin‐1 is a cholesterol‐binding membrane protein involved in cellular cholesterol transport and homeostasis. Evidence presented here demonstrates an up‐regulation of caveolin‐1 in the hippocampus, which was temporally correlated with an increase in synaptophysin during the reinnervation phase in a mouse model of hippocampal deafferentation. Using an in vitro model of neuronal reactive plasticity, we examined the effect of virally mediated overexpression of caveolin‐1 on injured differentiated PC12 cells undergoing terminal remodeling. Three days post lesion, caveolin‐1‐overexpressing cells revealed increases in synaptophysin and GAP‐43, two markers of neurite sprouting and synaptogenesis. Morphologically, caveolin‐1‐overexpressing cells showed a decrease in primary neurite outgrowth and branching as well as an increase in neurite density. Caveolin‐1‐overexpressing cells also revealed the presence of terminal swelling and beading along processes, consistent with a possible alteration of microtubules stability. Moreover, a focal enrichment of caveolin‐1 immunofluorescence was observed at the bases of axonal and dendritic terminals of mouse primary hippocampal neurons. Altogether, these results indicate that caveolin‐1 plays an active role in the regulation of injury‐induced synaptic and terminal remodeling in the adult CNS.