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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.

SUBMITTER: Almishaal A 

PROVIDER: S-EPMC8663027 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Role of cochlear synaptopathy in cytomegalovirus infected mice and in children.

Almishaal Ali A   Mathur Pranav Dinesh PD   Franklin Lesley L   Shi Kevin K   Haller Travis T   Martinovic Aleksandra A   Hirschmugl Kayla K   Earl Brian R BR   Zhang Chong C   Yang Jun J   Deans Michael R MR   Firpo Matthew A MA   Park Albert H AH  

International journal of pediatric otorhinolaryngology 20200804


<h4>Objectives</h4>Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy.<h4>Study design</h4>Murine model of CMV infection and case series.<h4>Subjects and methods</h4>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 ce  ...[more]

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