Characterizing Cytoskeleton Changes During Axonal Degeneration

BARABAS F; REMEDI MM; BARKER P; BISBAL M; STEFANI F; CACERES A; UNSAIN N

Mar de Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencias; 2015

Sociedad Argentina de Investigacion en Neurociencias

Axonal fragmentation is a regulated process that requires a growing set of receptors, signaling molecules, proteases and other regulators to disintegrate the axonal compartment. Little is known about the changes (and possible role) in the axonal cytoskeleton during degeneration. In this study we aimed at describing changes to the cytoskeleton during degeneration of sensory neurons axons grown in vitro and induced to degenerate 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 in deprivation and injury growth cone collapse (GCC) is almost completeat 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 use of drugs previously shown to prevent or delay degeneration. A global F-actin decrease was evident in every cell compartment during degeneration. Axonal microtubules form tight bundles and we observed early and marked de-bundling of these along degenerating axons. We are going to present preliminary data obtained using super-resolution STORM microscopy in order to unveil structural details with unprecedented resolution. Rather than being the last targets in the degenerative process, the early changes observed suggest that the axonal cytoskeleton has an instructive role in the subsequent fragmentation.