Animal models for studying motor axon terminal paralysis and recovery

Abstract

An extraordinary property of the peripheral nervous system is that nerve terminals can regenerate after damage caused by different physical, chemical, or biological pathogens. Regeneration is the result of a complex and ill-known interplay among the nerve, the glia, the muscle, the basal lamina and, in some cases, the immune system. This phenomenon has been studied using different injury models mainly in rodents, particularly in mice, where a lesion can be produced in a chosen anatomical area. These approaches differ significantly among them for the nature of the lesion and the final outcomes. We have reviewed here the most common experimental models employed to induce motor axon injury, the relative advantages and drawbacks, and the principal readouts used to monitor the regenerative process. Recently introduced tools for inducing reversible damage to the motor axon terminal that overcome some of the drawbacks of the more classical approaches are also discussed. Animal models have provided precious information about the cellular components involved in the regenerative process and on its electrophysiological features. Methods and tools made available recently allow one to identify and study molecules that are involved in the crosstalk among the components of the endplate. The time-course of the intercellular signaling and of the intracellular pathways activated will draw a picture of the entire process of regeneration as seen from a privileged anatomical site of observation.

Variability in venom composition of European viper subspecies limits the cross-effectiveness of antivenoms

“…The presence of PLA 2 components in its venom, encourages the idea that V . aspis neurotoxicity may be due to a SPAN-like toxin causing the degeneration of motor nerve terminals 16 , 18 – 20 , yet this possibility has never been investigated in detail. Degeneration of motor nerves can be easily monitored via neuromuscular junction (NMJ) immunohistochemistry 14 , 15 , 21 , 22 .…”

Signals Orchestrating Peripheral Nerve Repair

“…The NMJ, the specialized synapse controlling locomotion, is a privileged site of study of the cross talk driving nerve repair [96]. It is the site where the electric signal running along the motor axon is converted into a chemical one in the form of a released neurotransmitter (acetylcholine, ACh), which crosses the synaptic cleft and binds to muscle nicotinic ACh receptors, triggering muscle contraction [7].…”

Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells

“…H 2 O 2 is produced by mitochondria of damaged nerve terminals during degeneration caused by the presynaptic neurotoxin α-Latrotoxin (α-LTx), or by complement activation induced by presynaptic-binding autoantibodies (Duregotti et al 2015;Rodella et al 2016). Both agents cause a localized and reversible degeneration of motor axon terminals, and their action mimics the cascade of events that leads to nerve terminal degeneration in patients affected by different peripheral neuropathies (Duregotti et al 2015;Rodella et al 2016;Rigoni and Montecucco 2017). Neuronal H 2 O 2 rapidly diffuses across membranes and sets in motion a series of proregenerative responses in PSC, including a profound morphological remodeling (Duregotti et al 2015), which is likely to result from changes in transcribed and translated mRNAs.…”