title: Transient alteration of the vestibular calyceal junction and synapse in response to chronic ototoxic insult in rats.
abstract: Ototoxicity is known to cause permanent loss of vestibule function through degeneration of sensory hair cells (HCs). However, functional recovery has been reported during washout after chronic ototoxicity, although the mechanisms underlying this reversible dysfunction are unknown. Here, we study this question in rats chronically exposed to the ototoxic compound 3,3'-iminodipropionitrile (IDPN). Pronounced alterations in vestibular function appeared before significant loss of HCs or stereociliary coalescence became evident by ultrastructural analyses. This early dysfunction was fully reversible if the exposure was terminated promptly. In cristae and utricles, the distinct junctions formed between type I HCs (HCI) and calyx endings were completely dismantled at these early stages of reversible dysfunction, and completely rebuilt during washout. Immunohistochemical observations revealed loss and recovery of the junction proteins CASPR1 and tenascin-C and RT-PCR indicated that their loss was not due to decreased gene expression. KCNQ4 was mislocalized during intoxication and recovered control-like localization after washout. At early stages of the intoxication, the calyces could be classified as showing intact or lost junctions, indicating that calyceal junction dismantlement is triggered on a calyx-by-calyx basis. Chronic toxicity also altered the presence of ribeye, PSD-95 and GluA2 puncta in the calyces. These synaptic alterations varied between the two types of calyx endings (formed by calyx-only or dimorphic afferents) and some persisted at the end of the washout period. The present data reveal new forms of plasticity of the calyx endings in adult mammals, including a robust capacity for rebuilding the calyceal junction. These findings contribute to a better understanding of the phenomena involved in progressive vestibular dysfunction and its potential recovery during and after ototoxic exposure.
authors.affiliation: Departament de Ciències Fisiològiques II, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Sedó-Cabezón
authors.affiliation: Departament de Ciències Fisiològiques II, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Paulina
authors.initials: P
authors.lastname: Jedynak
authors.affiliation: Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, 17071 Girona, Catalonia, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Boadas-Vaello
authors.affiliation: Departament de Ciències Fisiològiques II, Universitat de Barcelona, 08907 L'Hospitalet de Llobregat, Catalonia, Spain Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 L'Hospitalet de Llobregat, Catalonia, Spain jllorens@ub.edu.
authors.forename: Jordi
authors.initials: J
authors.lastname: Llorens
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018069:Hair Cells, Vestibular / Q000473:pathology* / Q000648:ultrastructure; D051656:KCNQ Potassium Channels / Q000378:metabolism; D008297:Male; D009570:Nitriles; D020318:Rats, Long-Evans; D059547:Stereocilia / Q000473:pathology; D013569:Synapses / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism
chemical_list: D051656:KCNQ Potassium Channels; C492166:Kcnq4 protein, rat; D009570:Nitriles; D019063:Tenascin; C008110:3,3'-iminodipropionitrile
keywords: 3,3′-Iminodipropionitrile; CASPR1; Calyceal junctions; Calyx endings; Ototoxicity; Ribbon synapses; Vestibular system