Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/68492
Title: Transient alteration of the vestibular calyceal junction and synapse in response to chronic ototoxic insult in rats
Author: Sedó Cabezón, Lara
Jedynak, P.
Boadas i Vaello, Pere
Llorens i Baucells, Jordi
Keywords: Animals de laboratori
Equilibri (Fisiologia)
Toxicologia
Vertigen
Laboratory animals
Equilibrium (Physiology)
Toxicology
Vertigo
Issue Date: 2015
Publisher: The Company of Biologists
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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1242/dmm.021436
It is part of: Disease Models & Mechanisms, 2015, vol. 8, p. 1323-1337
Related resource: http://dx.doi.org/10.1242/dmm.021436
URI: http://hdl.handle.net/2445/68492
ISSN: 1754-8403
Appears in Collections:Articles publicats en revistes (Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB))
Articles publicats en revistes (Ciències Fisiològiques)

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