Naslov
TETANUS NEUROTOXIN ACTS AT THE NEUROMUSCULAR JUNCTION AND ON BRAINSTEM CENTERS THAT CONTROL MUSCLE MOVEMENT, RESPIRATION AND SWALLOWING IN A MURINE MODEL OF CEPHALIC TETANUS

Autori
Fabris, Federico ; Varani, S ; Tonellato, Marika ; Matak, Ivica ; Šoštarić, Petra ; Meglić, Patrik ; Simonato, Morena ; Rubini, A ; Caleo, Matteo ; Megighian, Aram ; Rossetto, Orenella ; Montecucco, Cesare ; Pirazzini, Marco

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
10TH CROATIAN CONGRESS OF PHARMACOLOGY AND THE 1ST CROATIAN CONGRESS OF CLINICAL PHARMACOLOGY WITH INTERNATIONAL PARTICIPATION / Mršić Pelčić, Jasenka ; Vitezić, Dinko ; Janković, Tamara - : Pharmaca, 2022, 180-180

Skup
10. hrvatski kongres farmakologije ; 1. hrvatski kongres kliničke farmakologije s međunarodnim sudjelovanjem = 10th Croatian Congress of Pharmacology ; 1st Croatian Congress of Clinical Pharmacology and Therapeutics with International Participation

Mjesto i datum
Opatija, Hrvatska, 22.09.2022. - 25.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
TeNT, cephalic tetanus, spasticity

Sažetak
Introduction: Tetanus is a neuroparalytic syndrome caused by Tetanus Neurotoxin (TeNT), the protein exotoxin produced by Clostridium tetani. The toxin enters in the cytosol of peripheral nerves to be then retrotransported to the central nervous system, where it enters inhibitory interneurons to cleave its target VAMP, thus preventing neurotransmission and leading to spastic paralysis. One of the most dangerous and less understood form of tetanus is cephalic tetanus (CT), that begins with an unusual facial palsy, and then evolves in the canonical spastic paralysis of facial muscles, dysphagia and a rapid failure of ventilation. The contrasting symptoms often postpone the correct diagnosis, making the prognosis poor. The molecular pathogenesis of these contrasting symptoms and why CT rapidly evolves into respiratory failure remain unresolved. Materials and Methods: We developed a CT model with local injections of TeNT in different muscles of mouse’s head. We then evaluated CT molecular pathophysiology by immunofluorescence and functional analyses (whisking, ventilation). Results: We report the unexpected finding that CT facial palsy is caused by VAMP proteolysis at the neuromuscular junction. This effect shadows the canonical central effect of TeNT, which however rapidly spreads to brainstem areas controlling critical functions, including mastication, deglutition and respiration. Conclusions: In addition to elucidating the molecular bases behind the unusual CT facial palsy, we unraveled why CT can rapidly evolve in a life- threatening form of tetanus and suggest that patients presenting to the emergency room with facial nerve palsy of unknown origin should be considered for CT and immediately hospitalized

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA