Characterizing cytoskeleton changes during axonal degeneration

BARABAS, F; REMEDI, M.; BISBAL, M.; BAKER, P; STEFANI, F.; CACERES, A.; UNSAIN, N.

Mar del Plata

Congreso; XXX Reunion Anual De La Sociedad Argentina De Investigacion En Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias - SAN -

Axonal fragmentation is a regulated process that requires a growing set of receptors,signaling molecules, proteases and other regulators to disintegrate the axonalcompartment. Little is known about the changes (and possible role) in the axonalcytoskeleton during degeneration. In this study we aimed at describing changes to thecytoskeleton during degeneration of sensory neurons axons grown in vitro and induced todegenerate by trophic factor withdrawal (?deprivation?) and axon transection (?injury?). We first focused our attention to the F-actin-rich growth cone and found that both indeprivation and injury growth cone collapse (GCC) is almost complete at early time points(3h of deprivation or 1h after injury), indicating an early remodeling of F-actin structures.To our surprise, GCC still took place when axonal fragmentation was prevented by the useof drugs previously shown to prevent or delay degeneration. A global F-actin decrease wasevident in every cell compartment during degeneration. Axonal microtubules form tightbundles and we observed early and marked de-bundling of these along degeneratingaxons. We are going to present preliminary data obtained using super-resolution STORMmicroscopy in order to unveil structural details with unprecedented resolution. Rather thanbeing the last targets in the degenerative process, the early changes observed suggest thatthe axonal cytoskeleton has an instructive role in the subsequent fragmentation.