Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus
Cephalic 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 spastic paralysis of tetanus, and rapid evolution of cardiorespiratory deficit even without genera...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-06-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.166978 |
| _version_ | 1797634284813549568 |
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| author | Federico Fabris Stefano Varani Marika Tonellato Ivica Matak Petra Šoštarić Patrik Meglić Matteo Caleo Aram Megighian Ornella Rossetto Cesare Montecucco Marco Pirazzini |
| author_facet | Federico Fabris Stefano Varani Marika Tonellato Ivica Matak Petra Šoštarić Patrik Meglić Matteo Caleo Aram Megighian Ornella Rossetto Cesare Montecucco Marco Pirazzini |
| author_sort | Federico Fabris |
| collection | DOAJ |
| description | Cephalic 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 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 vesicle-associated membrane protein within facial neuromuscular junctions and causes a botulism-like paralysis overshadowing tetanus spasticity. Meanwhile, TeNT spreads among brainstem neuronal nuclei and, as shown by an assay measuring the ventilation ability of CT mice, harms essential functions like respiration. A partial axotomy of the facial nerve revealed a potentially new ability of TeNT to undergo intra-brainstem diffusion, which allows the toxin to spread to brainstem nuclei devoid of direct peripheral efferents. This mechanism is likely to be involved in the transition from local to generalized tetanus. Overall, the present findings suggest that patients with idiopathic facial nerve palsy should be immediately considered for CT and treated with antisera to block the potential progression to a life-threatening form of tetanus. |
| first_indexed | 2024-03-11T12:05:28Z |
| format | Article |
| id | doaj.art-395ac61e128f4db1a549005bf0738965 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:05:28Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-395ac61e128f4db1a549005bf07389652023-11-07T16:25:42ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-06-01811Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanusFederico FabrisStefano VaraniMarika TonellatoIvica MatakPetra ŠoštarićPatrik MeglićMatteo CaleoAram MegighianOrnella RossettoCesare MontecuccoMarco PirazziniCephalic 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 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 vesicle-associated membrane protein within facial neuromuscular junctions and causes a botulism-like paralysis overshadowing tetanus spasticity. Meanwhile, TeNT spreads among brainstem neuronal nuclei and, as shown by an assay measuring the ventilation ability of CT mice, harms essential functions like respiration. A partial axotomy of the facial nerve revealed a potentially new ability of TeNT to undergo intra-brainstem diffusion, which allows the toxin to spread to brainstem nuclei devoid of direct peripheral efferents. This mechanism is likely to be involved in the transition from local to generalized tetanus. Overall, the present findings suggest that patients with idiopathic facial nerve palsy should be immediately considered for CT and treated with antisera to block the potential progression to a life-threatening form of tetanus.https://doi.org/10.1172/jci.insight.166978Neuroscience |
| spellingShingle | Federico Fabris Stefano Varani Marika Tonellato Ivica Matak Petra Šoštarić Patrik Meglić Matteo Caleo Aram Megighian Ornella Rossetto Cesare Montecucco Marco Pirazzini Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus JCI Insight Neuroscience |
| title | Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| title_full | Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| title_fullStr | Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| title_full_unstemmed | Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| title_short | Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| title_sort | facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus |
| topic | Neuroscience |
| url | https://doi.org/10.1172/jci.insight.166978 |
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