Role of cochlear synaptopathy in cytomegalovirus infected mice and in children.
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.
International journal of pediatric otorhinolaryngology
Animals; Auditory Threshold; Cochlea; Cytomegalovirus; Cytomegalovirus Infections; Evoked Potentials, Auditory, Brain Stem; Mice; Otoacoustic Emissions, Spontaneous
Cytomegalovirus; Murine; Sensorineural hearing loss; Synaptopathy
Almishaal, A., Mathur, P., Franklin, L., Shi, K., Haller, T., Martinovic, A., Hirschmugl, K., Earl, B. R., Zhang, C., Yang, J., Deans, M. R., Firpo, M. A., Park, A. H. Role of cochlear synaptopathy in cytomegalovirus infected mice and in children. International journal of pediatric otorhinolaryngology 138, 110275-110275 (2020).