Abstract
Hearing loss has become one of the most common disabilities worldwide. The synaptic connections between inner hair cells (IHCs) and spiral ganglion neurons have specialized synaptic constructions, termed ribbon synapses, which are important for auditory function. The ribbon synapses in the cochlea are quite vulnerable to various insults. As such, the maintenance of ribbon synapses is important for ensuring hearing function. Insulin-like growth factor 1 (IGF1) plays a critical role in the development and maintenance of the cochlea and has the potential to protect cochlear hair cells from various insults. In this study, we examined the role of IGF1 in the maintenance of ribbon synapses in cochlear explants of postnatal day four mice. We cultured cochlear explants with an IGF1 receptor antagonist, JB1, which is an IGF1 peptide analog. Results showed that exposure to JB1 for 24 h resulted in the loss of ribbon synapses. After an additional 24-h culture without JB1, the number of ribbon synapses spontaneously recovered. The application of exogenous IGF1 showed two different aspects of ribbon synapses. Low doses of exogenous IGF1 promoted the recovery of ribbon synapses, while it compromised the spontaneous recovery of ribbon synapses at high doses. Altogether, these results indicate that the paracrine or autocrine release of IGF1 in the cochlea plays a crucial role in the maintenance of cochlear ribbon synapses.
Highlights
Hearing loss has become one of the most common disabilities worldwide
All assays were performed using the middle portion (40–60% from the apex) of the cochlea because the numbers of ribbon synapses per Inner hair cell (IHC) varied according to the location in the cochlear turns (Meyer et al, 2009)
We quantified the number of CtBP2positive puncta and C-terminal-binding protein 2 (CtBP2) and glutamate receptor-2 (GluA2) co-stained puncta per IHC, respectively
Summary
Hearing loss has become one of the most common disabilities worldwide. The World Health Organization (2018) estimates that hearing loss affects over 6.1% (around 466 million people) of the world’s population. Hearing is a series of events in which sound vibrations travel into the cochlea and are converted into electrochemical signals that are perceived by the auditory cortex. The conversion is processed by mechanosensory hair cells (HCs) consisting. IGF1 on Cochlear Ribbon Synapses of outer and inner hair cells (IHCs). Outer hair cells (OHCs) act as motor units that amplify the sound stimuli and contact type II spiral ganglion neurons (SGNs). IHCs contact type I SGNs and convey electrochemical signals to the central auditory system (Hudspeth, 1997). Synaptic connections between IHCs and type I SGNs have specialized synaptic constructions, termed ribbon synapses, and are important for auditory function (Safieddine et al, 2012; Coate et al, 2019)
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