Thrombospondins 1 and 2 are important for afferent synapse formation and function in the inner ear. (27th January 2014)

• Record Type: Journal Article
• Authors: Mendus, Diana; Sundaresan, Srividya; Grillet, Nicolas; Wangsawihardja, Felix; Leu, Rose; Müller, Ulrich; Jones, Sherri M.; Mustapha, Mirna
• Is Part Of: European journal of neuroscience. Volume 39:Number 8(2014:Apr.)
• Page Start: 1256
• Page End: 1267
• Publication Date: 2014-01-27
• Subjects: Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.12486
• Languages: English
• ISSNs: 0953-816X

Abstract

<abstract abstract-type="main" id="ejn12486-abs-0001"> <title>Abstract</title> <p>Thrombospondins (TSPs) 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 TSP1 and TSP2 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 <italic>TSP1</italic>, <italic> TSP2</italic> and both (<italic>TSP1</italic>/<italic>TSP2</italic>) 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 <italic>TSP2</italic> and <italic>TSP1</italic>/<italic>TSP2</italic> knockout (KO) mice at postnatal day (P)29. In functional studies, <italic>TSP2</italic> and <italic>TSP1</italic>/<italic>TSP2</italic> 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 <italic>TSP1</italic>/<italic>TSP2</italic> KO mice. <italic>TSP1</italic>/<italic>TSP2</italic> KO mice also showed reduced wave I amplitudes of ABRs and vestibular evoked potentials, suggesting synaptic dysfunction in both the auditory and vestibular systems. Whereas ABR thresholds in <italic>TSP1</italic> KO mice were relatively unaffected at early ages, <italic>TSP1</italic>/<italic>TSP2</italic> 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 TSPs play an important role in afferent synapse development and function of the inner ear.</p> </abstract>