Naslov
Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus

Autori
Fabris, Federico ; Varani, Stefano ; Tonellato, Marika ; Matak, Ivica ; Šoštarić, Petra ; Meglić, Patrik ; Caleo, Matteo ; Megighian, Aram ; Rossetto, Ornella ; Montecucco, Cesare ; Pirazzini, Marco

Izvornik
JCI Insight (2379-3708) 9 (2023); E166978, 24

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Neurological disorders ; Neuromuscular disease ; Neuroscience ; Toxins/drugs/xenobiotics.

Sažetak
Ephalic tetanus (CT) is a severe form of tetanus that follows head wounds and the intoxication of cranial nerves by tetanus neurotoxin (TeNT). Hallmarks of CT are cerebral palsy, which anticipates the typical spastic paralysis of tetanus, and rapid evolution of cardiorespiratory deficit even without generalized tetanus. How TeNT causes this unexpected flaccid paralysis, and how the canonical spasticity then rapidly evolves into cardiorespiratory defects remain unresolved aspects of CT pathophysiology. Using electrophysiology and immunohistochemistry, we demonstrate that TeNT cleaves its substrate VAMP within facial neuromuscular junctions and causes a botulism-like paralysis overshadowing its canonical spasticity. Meanwhile, TeNT spreads among brainstem neuronal nuclei and, as shown by an assay to monitor the ventilation ability of CT mice, it harms essential functions like respiration. A partial axotomy of the facial nerve revealed a still-unknown ability of TeNT to undergo intra-brainstem diffusion, which allows the toxin to spread onto brainstem nuclei devoid of direct peripheral efferents. Other showing a mechanism possibly involved in the transition from local to generalized tetanus, these findings suggest that patients with idiopathic facial nerve palsy should be immediately considered for CT and treated with antisera to block the potential progression of a life-threatening form of tetanus.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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