Clin Exp Otorhinolaryngol.  2021 Feb;14(1):76-81. 10.21053/ceo.2019.01382.

MicroRNAs Related to Cognitive Impairment After Hearing Loss

• Mun SK
• Chae H
• Piao XY
• Lee HJ
• Kim YK
• Oh SH
• Chang M

• KMID: 2512884
• DOI: http://doi.org/10.21053/ceo.2019.01382

Abstract

Objectives
. Our research group has previously demonstrated that hearing loss might be a risk factor for synaptic loss within the hippocampus and impairment of cognition using an animal model of Alzheimer disease. In this study, after inducing hearing loss in a rat model of Alzheimer disease, the associations of various microRNAs (miRNAs) with cognitive impairment were investigated.
Methods
. Rats were divided randomly into two experimental groups: the control group, which underwent sham surgery and subthreshold amyloid-β infusion and the deaf group, which underwent bilateral cochlear ablation and subthreshold amyloid-β infusion. All rats completed several cognitive function assessments 11 weeks after surgery, including the object-in-place task (OPT), the novel object recognition task (NOR), the object location task (OLT), and the Y-maze test. After the rats completed these tests, hippocampus tissue samples were assessed using miRNA microarrays. Candidate miRNAs were selected based on the results and then validated with quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) analyses.
Results
. The deaf group showed considerably lower scores on the OPT, OLT, and Y-maze test than the control group. The microarray analysis revealed that miR-29b-3p, -30e-5p, -153-3p, -376a-3p, -598-3p, -652-5p, and -873-3p were candidate miRNAs, and qRT-PCR showed significantly higher levels of miR-376a-3p and miR-598-3p in the deaf group.
Conclusion
. These results indicate that miR-376a-3p and miR-598-3p were related to cognitive impairment after hearing loss.

Keyword

MicroRNA; Alzheimer Disease; Hearing Loss; Dementia; Hippocampus

Figure

• 

  Fig. 1. Auditory brainstem response (ABR) threshold results before cochlear ablation and 1, 6, and 11 weeks after surgery. (A) Control group (n=9). (B) Deaf group (n=9). The error bars indicate standard deviation. SPL, sound pressure level.

• 

  Fig. 2. Results of cognitive tests. The deaf group (n=9) had somewhat lower scores than the control group (n=9) on the object-inplace task (OPT), object location task (OLT), and Y-maze test. NOR, novel object recognition task. The error bars indicate standard error. ***P<0.001 between the groups according to the Mann-Whitney test.

• 

  Fig. 3. Quantitative reverse transcription-polymerase chain reaction of candidate microRNAs. The relative quantification (RQ) values of miR-376a-3p and miR-598-3p significantly differed between the control (n=6) and deaf (n=6) groups. The error bars indicate standard error. **P<0.01 between the groups according to the MannWhitney test.

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