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Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear
Author(s) -
Mendus Diana,
Sundaresan Srividya,
Grillet Nicolas,
Wangsawihardja Felix,
Leu Rose,
Müller Ulrich,
Jones Sherri M.,
Mustapha Mirna
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12486
Subject(s) - inner ear , cochlea , synapse , neuroscience , biology , thrombospondins , vestibular system , brainstem , microbiology and biotechnology , genetics , thrombospondin , metalloproteinase , matrix metalloproteinase
Thrombospondins ( TSP s) constitute a family of secreted extracellular matrix proteins that have been shown to be involved in the formation of synapses in the central nervous system. In this study, we show that TSP 1 and TSP 2 are expressed in the cochlea, and offer the first description of their putative roles in afferent synapse development and function in the inner ear. We examined mice with deletions of TSP 1 , TSP 2 and both ( TSP 1 / TSP 2 ) for inner ear development and function. Immunostaining for synaptic markers indicated a significant decrease in the number of formed afferent synapses in the cochleae of TSP 2 and TSP 1 / TSP 2 knockout ( KO ) mice at postnatal day (P)29. In functional studies, TSP 2 and TSP 1 / TSP 2 KO mice showed elevated auditory brainstem response ( ABR ) thresholds as compared with wild‐type littermates, starting at P15, with the most severe phenotype being seen for TSP 1 / TSP 2 KO mice. TSP 1 / TSP 2 KO mice also showed reduced wave I amplitudes of ABR s and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in TSP 1 KO mice were relatively unaffected at early ages, TSP 1 / TSP 2 KO mice showed the most severe phenotype among all of the genotypes tested, suggesting functional redundancy between the two genes. On the basis of the above results, we propose that TSP s play an important role in afferent synapse development and function of the inner ear.