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Updated: Dec 11, 2025
Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea
Published on: May 10, 2019
Role of cochlear synaptopathy in cytomegalovirus infected mice and in children
Ali Almishaal1, Pranav Dinesh Mathur2, Lesley Franklin3
1College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia.
Objectives:
Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy.
Study Design:
Murine model of CMV infection and case series.
Subjects And Methods:
C57 BL/6 mice were inoculated with murine-CMV (mCMV). Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Temporal bones from mCMV-infected mice were used for both ribbon synapse and hair cell quantification. Four groups of children (non-CMV normal hearing, non-CMV hearing impaired, CMV normal hearing and CMV hearing impaired) underwent ABRs between 2014 and 2018. The outcomes included raw amplitude, wave I:V amplitude ratio, absolute latency, and interpeak latency.
Results:
Mice at 8 weeks post mCMV infection had higher ABR and DPOAE (P < 0.05) thresholds and increased outer hair cell loss compared to uninfected mice and mCMV-infected mice at 4 and 6 weeks post infection, indicating progressive hearing loss. A reduction in the wave I amplitude and synaptic counts were noted earlier at 4 weeks in CMV-infected mice (P < 0.05). The human data indicated that the wave I:V amplitude ratio was lower on average in CMV-infected groups when compared to the uninfected cohorts. The wave I:V amplitude ratio for the click and 4k stimuli were not significantly different between the congenital CMV-infected and uninfected children with normal or with hearing loss.
Conclusion:
This study suggests mCMV infection results in a synaptopathy before hair cell damage. Additional studies need to be performed to determine whether this effect is also observed in CMV-infected children.
Level Of Evidence:
Animal studies and basic science- NA; human studies: level 4.
Insights
Murine cytomegalovirus (CMV) infection causes synaptopathy, a nerve disorder, before hair cell damage, leading to progressive hearing loss. Further research is needed to confirm this in infected children.
Area of Science:
- Neuroscience
- Otolaryngology
- Virology
Background:
- Cytomegalovirus (CMV) infection is a common cause of sensorineural hearing loss.
- Synaptopathy, a dysfunction of synapses, is increasingly recognized as a contributor to hearing impairment.
Purpose of the Study:
- To investigate the presence of synaptopathy in a murine model of CMV infection and in CMV-infected children.
- To determine if CMV infection impacts auditory nerve function and hair cell integrity.
Main Methods:
- A murine model of murine CMV (mCMV) infection was established. Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing.
- Temporal bones from infected mice were analyzed for ribbon synapse and hair cell counts. Human data from CMV-infected and uninfected children (normal hearing and hearing impaired) were analyzed using ABRs.
Main Results:
- Mice infected with mCMV exhibited progressive hearing loss, evidenced by elevated ABR and DPOAE thresholds and increased outer hair cell loss at 8 weeks post-infection.
- Synaptic changes, specifically reduced wave I amplitude and synaptic counts, were observed as early as 4 weeks post-mCMV infection.
- In human subjects, a trend towards a lower wave I:V amplitude ratio was observed in CMV-infected groups, suggesting potential auditory nerve involvement, though not statistically significant for all stimuli.
Conclusions:
- Murine CMV infection induces synaptopathy preceding hair cell damage, indicating a direct impact on auditory nerve function.
- The findings suggest that synaptopathy may be an early mechanism of hearing impairment in CMV infection.
- Further investigation is warranted to confirm the presence and extent of synaptopathy in CMV-infected children.
