Role of cochlear synaptopathy in cytomegalovirus infected mice and in children

Abstract

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.

Keywords: Cytomegalovirus; Murine; Sensorineural hearing loss; Synaptopathy.