Neuron-targeted caveolin-1 improves motor function and preserves memory in mice subjected to brain trauma

Author(s): Posadas, Edmund; Egawa, Junji; Schilling, Jan M.; Cui, Weihua; Sawadi, Atsushi; Alas, Basheer; Zemljic-Harpf, Alice E.; Fallon, McKenzie; Mandyam, Chitra D.; Roth, David M.; Patel, Hemal H.; Patel, Piyush M.; Head, Brian P. | Abstract: Studies in vitro and in vivo demonstrate that membrane/lipid rafts (MLR) and caveolin (Cav) organize pro-growth receptors, and when over-expressed specifically in neurons, Cav-1 augments neuronal signaling and growth, and improves cognitive function in adult and aged mice. However, whether Cav-1 overexpression can preserve motor and cognitive function in the setting of brain trauma is unknown. Here, we engineered a neuron-targeted Cav-1 overexpressing transgenic (Tg) mouse (via synapsin promoter, SynCav1 Tg) and subjected it to a controlled cortical impact (CCI) model of brain trauma and measured biochemical, anatomical, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav-1 and MLR-localization of PSF-95, NMDAR, and TrkB. When subjectd to CCI, SynCav1 Tg mice demonstrated preserved hippocampal-dependent fear learning and memory, motor function recovery on inverted grid, and decreased brain lesion volume. Conclusion: Neuron-targeted overexpression of Cav-1 in the adult brain preserves hippocampal-dependent learning and memory, restores motor function after brain trauam, and decreases brain lesion size. Our findings suggest neuron-targeted Cav-1 as a novel therapeutic strategy to restore nerve function and prevent trauma-associated neurodegeneration.