Modifications of the membrane-associated periodic skeleton (MPS) in axons during injury-induced axonal degeneration

GABY FABIANA MARTÍNEZ; NAHIR GUADALUPE GAZAL; GONZALO QUASSOLLO; THOMAS M DURCAN; ALFREDO CÁCERES; NICOLÁS UNSAIN

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Argentine Society for Research in Neuroscience

Axonal fragmentation is a regulated process that depends onvarious signaling molecules, proteases, and other regulatorsto actively disintegrate the axonal compartment. In thiswork, we studied the change and possible role of theaxonal membrane-associated periodic skeleton (MPS)during injury-induced degeneration. The injury model consistedon sensory neuron explants sections with a scalpelblade, producing axonal degeneration in the distal portion ofthe sectioned axons. The MPS is organized in periods of 190nm, hence unobservable by diffraction-limited conventionalfluorescence microscopy. Here, we used two differentsuper-resolution techniques: Expansion Microscopy (ExM)and Stimulated Emission Depletion Nanoscopy (STED).We show that the MPS abundance and organization decaysat an early time point after injury, well before the onset ofaxon fragmentation. In addition, pharmacological treatmentsthat prevent axonal fragmentation, such as NADþ, also preventearly loss of the MPS. We further show evidence demonstratingthe effect of dismantling the MPS with the actindepolymerization drug Latrunculin A on axonal fragmentationin control and injured axons. In summary, our worksuggests that the MPS is necessary for stabilization of theaxon compartment during injury-induced degeneration.