Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo
Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiolog...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-07-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/12/7/dmm039115 |
| _version_ | 1819159598199734272 |
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| author | Raphaelle Cassel Pierrick Bordiga Julie Carcaud François Simon Mathieu Beraneck Anne Le Gall Anne Benoit Valentine Bouet Bruno Philoxene Stéphane Besnard Isabelle Watabe David Pericat Charlotte Hautefort Axel Assie Alain Tonetto Jonas Dyhrfjeld-Johnsen Jordi Llorens Brahim Tighilet Christian Chabbert |
| author_facet | Raphaelle Cassel Pierrick Bordiga Julie Carcaud François Simon Mathieu Beraneck Anne Le Gall Anne Benoit Valentine Bouet Bruno Philoxene Stéphane Besnard Isabelle Watabe David Pericat Charlotte Hautefort Axel Assie Alain Tonetto Jonas Dyhrfjeld-Johnsen Jordi Llorens Brahim Tighilet Christian Chabbert |
| author_sort | Raphaelle Cassel |
| collection | DOAJ |
| description | Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients. |
| first_indexed | 2024-12-22T16:43:06Z |
| format | Article |
| id | doaj.art-a61921b5ef864496b340bb8918f08e13 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-22T16:43:06Z |
| publishDate | 2019-07-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-a61921b5ef864496b340bb8918f08e132022-12-21T18:19:49ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-07-0112710.1242/dmm.039115039115Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigoRaphaelle Cassel0Pierrick Bordiga1Julie Carcaud2François Simon3Mathieu Beraneck4Anne Le Gall5Anne Benoit6Valentine Bouet7Bruno Philoxene8Stéphane Besnard9Isabelle Watabe10David Pericat11Charlotte Hautefort12Axel Assie13Alain Tonetto14Jonas Dyhrfjeld-Johnsen15Jordi Llorens16Brahim Tighilet17Christian Chabbert18 Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France Integrative Neuroscience and Cognition Center, UMR 8002, CNRS, 75006 Paris, France INSERM U1075, Caen, France INSERM U1075, Caen, France INSERM U1075, Caen, France INSERM U1075, Caen, France INSERM U1075, Caen, France Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Hôpital Lariboisière, 75010 Paris, France Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France Aix-Marseille Université, CNRS, Centrale Marseille, FSCM (FR1739), PRATIM, Marseille, 13000 France Sensorion, Montpellier, 34000 France Universitat de Barcelona, 08907 Barcelona, Spain Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Aix Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Sensorielles et Cognitives - Equipe Physiopathologie et Thérapie des Désordres Vestibulaires, Marseille, 13000 France Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients.http://dmm.biologists.org/content/12/7/dmm039115VestibuleSynapsesExcitotoxicityPlasticityVestibular disorders |
| spellingShingle | Raphaelle Cassel Pierrick Bordiga Julie Carcaud François Simon Mathieu Beraneck Anne Le Gall Anne Benoit Valentine Bouet Bruno Philoxene Stéphane Besnard Isabelle Watabe David Pericat Charlotte Hautefort Axel Assie Alain Tonetto Jonas Dyhrfjeld-Johnsen Jordi Llorens Brahim Tighilet Christian Chabbert Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo Disease Models & Mechanisms Vestibule Synapses Excitotoxicity Plasticity Vestibular disorders |
| title | Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo |
| title_full | Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo |
| title_fullStr | Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo |
| title_full_unstemmed | Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo |
| title_short | Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo |
| title_sort | morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute onset vertigo |
| topic | Vestibule Synapses Excitotoxicity Plasticity Vestibular disorders |
| url | http://dmm.biologists.org/content/12/7/dmm039115 |
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