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논문 기본 정보

자료유형
학술저널
저자정보
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대한이비인후과학회 Clinical and Experimental Otorhinolaryngology Clinical and Experimental Otorhinolaryngology 제12권 제1호
발행연도
2019.1
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33 - 39 (7page)

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Objectives. Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-β signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. Methods. The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. Results. Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. Conclusion. Losartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity.

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참고문헌 (19)

참고문헌 신청
Wu C / 2016 / Tinnitus : maladaptive auditory-somatosensory plasticity / Hear Res 334:20~29 google schola Zhan X / 2006 / Projections of the second cervical dorsal root ganglion to the cochlear nucleus in rats / J Comp Neurol 496(3):335~348 google schola Zhou J / 2006 / Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the guinea pig / J Comp Neurol 495(1):100~112 google schola Dehmel S / 2012 / Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus: possible basis for tinnitus-related hyperactivity? / J Neurosci 32(5):1660~1671 google schola Koehler SD / 2013 / Stimulus timing-dependent plasticity in dorsal cochlear nucleus is altered in tinnitus / J Neurosci 33(50):19647~19656 google schola

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